Nutrients doi: 10.3390/nu18213536

Authors: Yu Liu Benkang Su Minghui Yang Bingqing Shang Yue Geng Qiu Wu

Background: Alcoholic fatty liver disease (AFLD) represents an early, reversible stage within the spectrum of alcoholic liver disease. Palmitoleic acid (POA), classified as an ω-7 MUFA, has previously demonstrated hepatoprotective properties against non-alcoholic fatty liver disease, but the protective effect of it in AFLD and its impact on the intestinal flora and metabolites remain unclear. The research sought to elucidate the protective role of POA in AFLD in a murine model and corresponding mechanistic pathways. Methods: Thirty male Kunming mice were randomly distributed across five experimental cohorts: a healthy control group, an alcohol-exposed model group, and three POA-treated groups receiving daily different doses. With the exception of the control cohort, all animals underwent intragastric administration of 53% ethanol once daily. Multiple endpoints were evaluated, including hepatic function markers, lipid metabolic profiles, antioxidant capacity, liver histopathological features, colonic microbial composition, and intestinal metabolomic signatures. Results: Our findings revealed that POA supplementation markedly lowered hepatic and serum concentrations of ALT, AST, TBA, AKP, TBIL, TP, Alb, and MDA, while it concurrently returned HDL-C and TG levels, thereby effectively counteracting alcohol-triggered hepatic injury. Moreover, POA mitigated alcohol-associated gut microbial imbalance by decreasing Firmicutes/Bacteroidetes and remodeled the relative abundances of Turicibacter, Prevotellaceae UCG-001, Akkermansia and Bacteroides. Metabolomic profiling further demonstrated that POA normalized perturbed levels of Hispidol, Suberosin, Val-Trp-His, and N-acetylserine and influenced metabolic pathways related to digestion, lipid processing, and amino acid turnover. Correlation analyses validated robust interrelationships among key differential bacterial taxa, altered metabolites, and hepatic injury biomarkers in AFLD mice. Conclusions: In conclusion, POA exerts a protective effect against AFLD in mice, and this hepatoprotective effect is associated with the amelioration of gut dysbiosis and the restoration of intestinal metabolic profiles. These findings provide preliminary scientific evidence for the development of POA as a functional food ingredient for AFLD prevention and control.

Nutrients doi: 10.3390/nu18213535

Authors: Francesca Gorini Alessandro Tonacci Morena Gabriele Andrea Borghini

Irritable bowel syndrome (IBS) is one of the most common disorders of gut–brain interaction, and dietary interventions play a central role in symptom management. Among these, the low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (low-FODMAP) diet has been shown to improve abdominal pain, bloating, and altered bowel habits in a substantial proportion of patients. However, restriction of fermentable carbohydrates may reduce the availability of substrates for the gut microbiota and has been associated with reductions in selected microbial taxa, including Bifidobacterium, raising questions about its effects on microbial ecology and metabolism. Dietary prebiotics selectively stimulate gut microorganisms and promote microbial fermentation and the production of metabolites, including short-chain fatty acids, that may contribute to intestinal homeostasis. However, many prebiotics are also highly fermentable substrates, and their gastrointestinal effects may vary substantially among individuals with IBS. This creates a challenge in balancing symptom control with continued exposure to substrates that may support microbial and metabolic functions. In this narrative review, we critically examine the metabolic and clinical implications of dietary prebiotics in IBS, with particular emphasis on their potential role following low-FODMAP restriction. We discuss their effects on gut microbiota composition and function, microbial metabolites, and clinically relevant outcomes, with particular attention to the relationship between microbial and symptomatic responses. We further consider the potential role of structured reintroduction and personalization of tolerated fermentable substrates in maintaining dietary variety and microbial substrate availability while minimizing gastrointestinal symptoms. Finally, we discuss interindividual variability in responses to fermentable substrates and factors that may contribute to differential responses, highlighting current limitations in linking microbiota composition, microbial function, metabolite production, and clinical outcomes in IBS, and identifying possible directions for future research.

Nutrients doi: 10.3390/nu18213534

Authors: Martín Campuzano-Donoso Claudia Reytor-González Gerardo Sarno Martha Montalvan Luigi Barrea Giovanna Muscogiuri Ludovica Verde Giuseppe Annunziata Daniel Simancas-Racines

We thank the authors for their Comment [...]

Nutrients doi: 10.3390/nu18213533

Authors: Magnus Strømmen Ragnhild Bergene Skråstad

The review by Campuzano-Donoso et al [...]

Nutrients doi: 10.3390/nu18213532

Authors: Abelardo Cesar Avila-Curiel Teresa Shamah-Levy Elsa Berenice Gaona-Pineda Marco Antonio Avila-Arcos Marti Yareli Del Monte-Vega Lucia Cuevas-Nasu Ignacio Méndez Gómez-Humarán

Background/Objectives: Childhood body mass index (BMI) is dynamic, and cross-sectional estimates do not capture within-child changes over time. This study aimed to characterize longitudinal BMI-for-age trajectories among Mexican school-aged children and examine differences according to individual and school-context characteristics. Methods: We analyzed 463,244 children aged 5–12 years with valid anthropometric measurements over four consecutive school years (2015–2016 to 2018–2019). BMI-for-age z-scores (BAZ) were calculated using the WHO 2007 growth reference. Longitudinal patterns were identified using latent class mixed models. Multinomial logistic regression estimated the proportions of children belonging to each trajectory group, and population-averaged generalized estimating equations (GEE) examined overweight/obesity across school grades and trajectory groups. Results: Four trajectories were identified, broadly corresponding to low-BAZ, mid-range BAZ, elevated BAZ, and very-high BAZ trajectories, comprising 13.08%, 43.68%, 32.01%, and 11.23% of children, respectively. Trajectory-group membership probabilities differed by sex and school-context characteristics. Girls had a higher proportion in the mid-range BAZ trajectory than boys (45.7 vs. 41.7%) but a lower one in the very-high BAZ trajectory (8.4 vs. 14.0%). Elevated BAZ and very-high BAZ trajectory proportions increased as municipal marginalization decreased. In the GEE model, overweight/obesity increased across school grades, particularly in the elevated BAZ trajectory (grade-by-trajectory interaction (OR = 1.33; p < 0.001); girls had lower (OR = 0.94; p < 0.001) and children attending urban schools higher (OR = 1.1; p < 0.001) overweight/obesity. Conclusions: Mexican school-aged children exhibited heterogeneous longitudinal BMI-for-age patterns. Individually linked repeated anthropometric measurements provide information on within-child BMI patterns that complement cross-sectional prevalence estimates and may improve the characterization of childhood nutritional status across school and geographic contexts.

Nutrients doi: 10.3390/nu18213531

Authors: Nouf Aljawini Syed Shahid Habib Khalid Al-Regaiey

Background: Irisin is an exercise-induced myokine also produced by adipose tissue and thus considered an adipo-myokine. Its relationship with adiposity and sarcopenia-related indices remains unclear. We examined these associations and compared circulating irisin concentrations across operationally defined phenotypes in premenopausal and postmenopausal women. Methods: In this cross-sectional study, 79 women underwent body-composition assessment by BIA and HGS measurement by dynamometry, of whom 78 underwent serum irisin measurement by ELISA. Participants were classified into four operational phenotypes (Control, Obesity, Sarcopenia, and Sarcopenic Obesity) using BMI ≥ 30 kg/m2 for obesity and HGS < 16 kg for low muscle strength. Irisin was compared across phenotypes and correlated with adiposity and sarcopenia-related indices. Results: Circulating irisin was significantly lower in women with BMI-defined obesity than in those without obesity (173.70 [89.03–357.20] vs. 347.30 [188.90–716.00] pg/mL; p = 0.0024) but did not differ when obesity was defined by %BF (≥35%; p = 0.1034). Overall, irisin did not differ by menopausal status. Among postmenopausal women, irisin concentrations were lower in those with obesity than in those without obesity (179.70 [85.30–321.90] vs. 403.60 [219.20–801.70] pg/mL; p = 0.0043), whereas no significant difference was observed among premenopausal women (p = 0.2666). Across the operational phenotypes, irisin was lowest in the sarcopenic obesity group (128.90 [68.57–321.90] pg/mL) and significantly lower than in controls (322.40 [164.10–498.40] pg/mL; p = 0.0076). Irisin was not significantly associated with HGS, ASM, or MQI, whereas ASMI showed an inverse association (r = −0.2773, p = 0.0153). Significant inverse associations were observed with FMI (r = −0.3835, p = 0.0006), BMI (r = −0.3609, p = 0.0013), and %BF (r = −0.3396, p = 0.0025). In exploratory univariable regression analyses, BMI, FMI, and %BF accounted for 15.9%, 15.2%, and 8.4% of the variance in circulating irisin, respectively. Conclusions: Circulating irisin showed consistent inverse associations with adiposity indices but a less consistent pattern across muscle-related indices, suggesting that adiposity may be particularly relevant to circulating irisin in women.

Nutrients doi: 10.3390/nu18213530

Authors: Ryuji Takeda Akiyoshi Sawabe

Interindividual variability in response to dietary and functional food interventions is increasingly being recognized as a central issue in precision nutrition. However, individuals showing large pre–post changes are frequently classified as responders without adequately considering measurement error, within-person biological variability, regression to the mean, or distinction between the observed outcome variability and true heterogeneity in treatment effect. This review critically examines responder and non-responder concepts in functional food and dietary intervention trials, focusing on statistical interpretation, clinical trial design, biological determinants, metabolomics, metabotyping, multi-omics integration, and machine-learning approaches. We highlight the limitations of threshold-based responder classification, separate within-group significance testing, post hoc subgroup analyses, and high-dimensional predictive models without appropriate validation. Evidence from representative intervention studies is organized along a progression from retrospective responder classification and biological characterization to baseline predictor identification, predictive modeling, external validation, and prospective response-guided intervention. Particular attention is given to the distinction between explaining why individuals appeared to respond and predicting response before intervention. Based on the methodological and empirical evidence reviewed, we propose a structured hierarchy for responder research, ranging from descriptive heterogeneity to prospective response-guided intervention. The key challenge for precision nutrition is therefore not simply to identify who appeared to respond, but to determine whether heterogeneous responses are reproducible, treatment-specific, prospectively predictable, and useful for improving intervention selection. Moving from retrospective classification toward validated prospective prediction will be essential for translating responder research in functional foods into rigorous and clinically meaningful precision nutrition.

Nutrients doi: 10.3390/nu18213529

Authors: Evridiki Patelarou Konstantinos Giakoumidakis

Chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, obesity, and chronic kidney disease, are the leading causes of morbidity and mortality worldwide [...]

Nutrients doi: 10.3390/nu18213528

Authors: Alba Zabalegui-Eguinoa Fernanda Mucarzel-Suarez-Arana Raül Cartiel-Vesperinas Cora Oliver-Vila Marta Ricart-Viles Laura Andurell-Ferrandiz Amador Lluch-Romero Albert Puig-Perez Fiorella Palmas Rosa Burgos-Peláez

Background & Aims: Accurate assessment of hydration status is particularly relevant in hospitalized patients receiving parenteral support in whom fluid disturbances are common and may be associated with adverse outcomes. However, the prognostic significance of bioimpedance-derived hydration status in the population receiving parenteral nutrition (PN) remains poorly defined. This study aimed to evaluate the association between hydration status at the beginning of PN and in-hospital mortality. Methods: This single-center prospective observational cohort included hospitalized adults receiving PN between November 2024 and March 2026. Hydration status was assessed within 72 h of PN initiation using bioelectrical impedance analysis (Hydragram®, Akern). Receiver operating characteristic (ROC) analysis was used to identify the optimal hydration threshold for in-hospital mortality prediction. Survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards models. Results: A total of 276 patients were included (62.0% male; mean age 64.9 ± 17.5 years). Overall in-hospital mortality was 13.4%. Hydration percentage showed good discrimination for in-hospital mortality (AUC 0.776, 95% CI 0.672–0.880; p < 0.001), with an optimal cut-off value of 79.45%. Patients with overhydration exhibited higher mortality rates than normohydrated patients (29.3% vs. 5.4%; log-rank p < 0.001). In multivariable Cox regression analysis, overhydration remained independently associated with in-hospital mortality (HR 2.85, 95% CI 1.21–6.70; p = 0.016), together with age (HR 1.06, 95% CI 1.02–1.10; p = 0.002). Bioelectrical impedance vector analysis (BIVA) demonstrated a clustering of non-survivors in vector regions consistent with extracellular fluid expansion. Conclusions: Overhydration assessed by bioelectrical impedance analysis was independently associated with in-hospital mortality in patients receiving PN. Early assessment of hydration status by bioelectrical impedance may provide clinically relevant information for risk stratification in hospitalized patients receiving parenteral nutrition.

Nutrients doi: 10.3390/nu18213527

Authors: Adrian Kwaśny Małgorzata Słoma-Krześlak Izabella Uchmanowicz Christopher S. Lee Ercole Vellone Raúl Juárez-Vela Stanisław Surma Mateusz Labudda Michał Czapla

Frailty is highly prevalent in patients with heart failure (HF) and frequently coexists with malnutrition, sarcopenia, cachexia, and obesity, creating substantial challenges for nutritional assessment and management. These conditions overlap clinically but represent distinct biological phenotypes and should not be treated as interchangeable constructs. This narrative review critically synthesizes current evidence on nutritional care in patients with HF and frailty, focusing on nutritional assessment, energy and protein requirements, areas of alignment and conflict between HF- and frailty-oriented recommendations, and the effects of nutritional interventions on frailty-related outcomes. Nutritional assessment should be multidimensional, as congestion, inflammation, altered body composition, and renal dysfunction may limit the interpretability of body weight, BMI, biochemical indices, and screening tools. Current recommendations for energy and protein intake remain largely extrapolated from geriatric, multimorbidity, renal, or general HF populations, and no universally validated targets exist for frail patients with HF. Dietary management therefore requires balancing potentially competing priorities, including congestion control, preservation of muscle mass and function, adequate nutrient intake, renal limitations, and, in obesity-related HF, intentional fat loss without excessive loss of lean tissue. Available interventional evidence suggests that individualized nutritional support may improve nutritional status and selected functional outcomes, but effects on frailty as an integrated syndrome remain uncertain. Overall, nutritional care in HF with frailty should move towards phenotype-directed, multidisciplinary strategies integrating nutrition, physical activity, rehabilitation, and longitudinal assessment. Future trials should standardize frailty definitions, clinically relevant outcomes, and nutrition-related targets.

Nutrients doi: 10.3390/nu18213526

Authors: Nur Ecem Baydı Ozman Can Gönen Cansu Gençalp Meryem Kahrıman Aydemir Murat Baş

Background/Objectives: Dietary interventions are central to irritable bowel syndrome (IBS) management, but evidence directly comparing a low-FODMAP diet (LF), adapted NICE dietary advice (NICE), and adapted NICE dietary advice combined with intermittent fasting (NICE–IF) is limited. This study compared the short-term effects of LF, NICE, and NICE–IF on IBS symptom severity and disease-specific quality of life. Methods: In this prospective, three-arm, non-randomized controlled dietary intervention study, adults with IBS followed LF, NICE, or NICE–IF for two weeks. IBS symptom severity, disease-specific quality of life, and psychological status were assessed using the Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS), the IBS Quality of Life questionnaire (IBS-QOL), and the Hospital Anxiety and Depression Scale (HADS), respectively, at baseline and after the two-week intervention; stool consistency was monitored using the Bristol Stool Form Scale (BSFS). Between-group differences were additionally examined using analysis of covariance (ANCOVA) adjusted for baseline values. Results: Eighty-one participants completed the study. IBS symptom severity decreased significantly in all groups (all p < 0.001), with a significant between-group difference in change (p = 0.018); the reduction was greater with LF than with NICE (p = 0.017). IBS-specific quality of life improved significantly in all groups (all p ≤ 0.002). Although the overall change differed among groups (p = 0.012), pairwise differences were not significant. After adjustment for baseline values, no significant between-group differences remained for symptom severity (p = 0.294) or quality of life (p = 0.333). Post-intervention stool consistency did not differ among groups (p = 0.485). A significant within-group reduction in anxiety scores was observed only in the NICE group (p = 0.025). Conclusions: All three interventions were associated with short-term improvements in IBS symptoms and quality of life. The greater unadjusted reduction in overall symptom severity with LF than with NICE was not robust to adjustment for baseline severity, and no between-group differences in quality-of-life improvement were observed; these findings require confirmation in larger, fully randomized studies with longer follow-up.

Nutrients doi: 10.3390/nu18213525

Authors: Zhenzhen Peng Yingjiao Deng Du Zhang Yaocheng Luo Ya Shi Huaping Wang Zumin Shi Yong Zhao

Background: Excessive salt intake is a major modifiable risk factor for hypertension and cardiovascular diseases. Caregivers of preschool children play an important role in shaping children’s dietary behaviors. This study aimed to evaluate the effectiveness of salt-reduction health education short videos in improving salt-related knowledge, attitudes, and practices (KAP) among caregivers of preschool children. Methods: This study enrolled 1038 caregivers of preschool children who were categorized into a short-video intervention group, a print media group, and a control group. The short-video and print media groups received a one-week salt-reduction health education intervention, whereas the control group received no additional intervention. KAP scores were assessed at pre-intervention, 1 week post-intervention, and 2 months post-intervention. Linear mixed-effects models, multivariable linear regression, and subgroup analyses were conducted to evaluate intervention effects. Results: In the linear mixed-effects model analysis, the short-video intervention group showed significantly greater increases in total KAP scores at 1 week post-intervention (β = 5.87, 95% CI: 4.30–7.43, p < 0.001) and 2 months post-intervention (β = 4.03, 95% CI: 2.46–5.60, p < 0.001). In the fully adjusted multivariable linear regression analysis, the short-video intervention group had significantly higher total KAP scores than the control group at 1 week post-intervention (β = 7.25, 95% CI: 5.66–8.84, p < 0.001) and 2 months post-intervention (β = 5.26, 95% CI: 3.56–6.97, p < 0.001). Subgroup analyses revealed that the short-video intervention group had significantly higher total KAP scores and domain-specific scores in most subgroups at 1 week and 2 months post-intervention. Conclusions: Salt-reduction health education short videos showed greater improvements in salt-related KAP among caregivers of preschool children than the print media intervention, although these differences cannot be attributed solely to the information delivery format, and short videos remain a promising strategy for salt-reduction education.

Nutrients doi: 10.3390/nu18213524

Authors: Nazanin Zakeri Liisa Tolvanen

Background/Objectives: Semaglutide is one of the currently widely used medications that have shown particularly strong effects on glycemic control and body weight in people with obesity and diabetes. However, gastrointestinal adverse effects are common during semaglutide therapy. Gut microbiota and probiotic supplementation have also attracted growing interest because of their potential effects on metabolic health and gastrointestinal function and their ability to support gastrointestinal health. Methods: This narrative review article investigated the potential interaction between probiotics and semaglutide in relation to gut microbiota, gastrointestinal function, and metabolic health. Results: Patients with metabolic disorders, including type 2 diabetes and obesity, commonly have gut dysbiosis, characterized by an imbalance in the composition and function of the intestinal microbiota. Semaglutide, as a currently important treatment for metabolic disorders, provides effective glycemic control and clinically meaningful weight loss; however, gastrointestinal adverse events are among the most frequently reported adverse effects of semaglutide treatment. Modulation of the gut microbiota may contribute to improved metabolic outcomes and gastrointestinal function. Probiotics may further modulate the gut microbiota by restoring microbial homeostasis, increasing the abundance of beneficial microorganisms, and improving microbial diversity. In addition, probiotic supplementation has been associated with improved metabolic outcomes, including better glycemic control in individuals with diabetes. Conclusions: Probiotics may potentially complement the metabolic effects of semaglutide and support gastrointestinal function and gut microbiota during semaglutide therapy. However, further studies are required to determine whether a clinically meaningful interaction exists between semaglutide and probiotics.

Nutrients doi: 10.3390/nu18213523

Authors: Roxana Elena Gheorghita Delia Viola Reurean Pintilei Olga Adriana Caliman Sturdza Roxana Filip Alina Crina Muresan Monica Iavorschi Ioan Ovidiu Sirbu

Background: Probiotic-enriched foods represent a promising nutritional approach for supporting health in chronic metabolic diseases. Yogurt provides a suitable food matrix for probiotic incorporation, while microencapsulation may improve probiotic stability during storage and consumption. Methods: The aim of this study was to develop and characterize a yogurt containing encapsulated Lacticaseibacillus rhamnosus (L. rhamnosus) and Bacillus clausii (B. clausii) and to evaluate its effects on selected dimensions of health-related quality of life (HRQoL) in patients with type 2 diabetes mellitus (T2DM). A probiotic-enriched yogurt was prepared using alginate–starch capsules containing L. rhamnosus and B. clausii. The product was evaluated during three weeks of refrigerated storage for pH, syneresis, water holding capacity, color, and probiotic viability. A randomized, two-arm, placebo-controlled interventional study was conducted in patients with T2DM. Participants received either probiotic yogurt containing encapsulated probiotics or a placebo yogurt containing probiotic-free capsules. HRQoL was assessed at baseline and post-intervention using the RAND 36-Item Health Survey (RAND 36). Results: During three weeks of refrigerated storage, the yogurt showed a progressive decrease in pH and syneresis, while water holding capacity remained indicative of good structural stability. Only minor changes in color were observed, and culturable microorganisms remained recoverable from the capsules during refrigerated storage. In an exploratory, placebo-controlled pilot evaluation, 54 patients with T2DM received two 100 g servings per week for three weeks. After Holm correction for multiple comparisons, the group × time interaction remained significant for vitality (adjusted p = 0.004) and emotional well-being (adjusted p = 0.009) but not for physical role limitations; in baseline-adjusted ANCOVA (Analysis of Variance), emotional well-being showed the most consistent evidence (adjusted difference 8.3 points, 95% CI 3.5–13.2), whereas results for vitality and physical role limitations were sensitive to model specification. Conclusions: Baseline HRQoL was substantially higher in the probiotic group, limiting causal interpretation. The yogurt showed favorable technological stability with culturable microorganisms persisting in the capsules during storage; the preliminary HRQoL signal requires confirmation in an adequately powered trial.

Nutrients doi: 10.3390/nu18213522

Authors: Sara Naseer Wai-Yann Tan Yin-Teng Sow Zhi-Yin Wai Sahana-Shri Ramanitharan Paey-Ern Bay Ching-Hsein Chen Soi-Moi Chye

Background/Objectives: Cancer recurrence and drug resistance arise from tumour-cell plasticity and microenvironmental adaptations that may persist after treatment. Cancer stem cells (CSCs) are associated with self-renewal, tumour initiation, residual disease, and treatment tolerance, whereas cellular senescence has context-dependent effects. Although therapy-induced senescence may restrict tumour-cell proliferation, persistent senescent tumour or stromal cells and their senescence-associated secretory phenotype (SASP) can, in selected models, promote inflammatory signalling, stemness-associated phenotypes and therapeutic resistance. This narrative review critically evaluates preclinical and translational evidence concerning curcumin, resveratrol, epigallocatechin gallate, berberine, piperine and shikonin as potential adjunctive modulators of CSCs and senescence-associated processes. Methods: Relevant literature was identified through searches of the MEDLINE/PubMed database from June 2000 and July 2026, using terms related to plant-derived bioactive compounds, CSCs, cellular senescence, SASP, recurrence and drug resistance. Evidence was evaluated according to model relevance, exposure, functional validation and whether it represented direct cross-axis evidence, intermediate mechanistic evidence, or marker- and pathway-level support. Results: Most studies examined CSCs and senescence as separate processes. Direct evidence showing that the same compound, within the same cancer model, modifies a validated cancer stem-cell function and a defined senescence or SASP and subsequently reduces resistance or recurrence is limited or absent. Moreover, poor bioavailability, variable formulations, potentially unachievable experimental exposures, drug interactions, tumour heterogeneity and limited clinical evidence constrain translation. Conclusions: Future studies should incorporate pharmacologically relevant exposures, functional and longitudinal endpoints, causal validation and biomarker-guided combination designs to determine whether these compounds can safely complement standard anticancer therapies.

Nutrients doi: 10.3390/nu18213521

Authors: Hanchen Lin Huanling Yu Min Gao

Objectives: Selenium and iodine are essential trace elements whose requirements increase during pregnancy, jointly regulating thyroid function and placental homeostasis. While their individual effects have been extensively studied, the evidence on combined Se–I exposure and their underlying molecular interactions remains fragmented. This scoping review aimed to map the gestational dynamics of maternal selenium and iodine status, synthesize the evidence linking their independent and joint effects to perinatal outcomes, and summarize their potential interacting mechanisms. Methods: Following the PRISMA-ScR guidelines, PubMed, Web of Science, and Scopus were searched from 2016 to September 2026. Studies were eligible if they assessed maternal selenium and/or iodine status in pregnant women or mother–infant pairs and reported outcomes related to thyroid function, placental homeostasis, pregnancy complications, fetal development, or long-term offspring health. Data were charted using a standardized form and synthesized descriptively by nutrient exposure, biological axis, and outcome domain. Results: Of the 2198 records identified, 91 studies met the eligibility criteria (36 selenium-only, 53 iodine-only, and 2 combined Se–I). Evidence indicates that mild-to-moderate isolated or combined selenium and iodine deficiencies remain common in pregnancy and are associated with adverse perinatal outcomes. Mechanistic studies, largely from in vitro and animal models, support multi-level biological interactions between selenium and iodine in thyroid hormone activation, antioxidant pathways, and placental–maternal interface regulation. However, population-based evidence on combined exposure remains scarce, and no randomized controlled trial has evaluated the incremental clinical benefit of combined supplementation. Conclusions: Maternal selenium and iodine status are interrelated determinants of thyroid and placental function during pregnancy. Combined Se–I deficiency may be associated with a greater risk of adverse maternal and infant outcomes through overlapping and potentially interacting mechanisms; however, human evidence is insufficient to establish synergy. Future large-scale prospective cohorts and baseline-stratified randomized trials are urgently needed to establish an evidence base for status-guided integrated micronutrient screening and precision nutritional management during pregnancy.

Nutrients doi: 10.3390/nu18213520

Authors: Chenchen Li Shuying Zhao Wei Mi Zhiyong Hu Tala Shi

Background: Dietary intervention could modulate gut microbiota, improve insulin resistance status, and play a key role in blood glucose regulation. Objective: This study investigated the regulatory effects of paeonidin- and cyanidin-rich fractions (PCs) on gut microbiota and serum metabolites in high-fat, high-sucrose diet/streptozotocin-induced type 2 diabetes mellitus (T2DM) rats. Method: Following a 14-day intragastric PC administration (25 mg/kg/day), non-targeted metabolomics and 16S rDNA sequencing were performed. Results: PC intervention significantly reduced water intake, and even the effects on lipids were limited. Among 83 differential serum metabolites, PC restored 28, including tauroursodeoxycholic acid (TUDCA) and lysophosphatidylcholines, while decreasing glycated branched-chain amino acid derivatives. PC-enriched Bifidobacterium, Sediminibacterium, SC-I-84, and Fusicatenibacter, which positively correlated with TUDCA. Additionally, PC upregulated insulin secretion and p53 signaling pathways with increased RYR2 and FAS, while downregulating pentose and glucuronate interconversion enzymes (UxaC, XylB). Conclusions: These findings suggest that the amelioration of glycolipid metabolic disorders and insulin secretion defects by PC may be associated with a synergistic gut microbiota-metabolite-enzyme axis, potentially involving Bifidobacterium-mediated TUDCA elevation and downstream modulation of metabolic enzymes.

Nutrients doi: 10.3390/nu18213519

Authors: Alondra Mora-Jiménez Wendy Campos-Perez Erika Martinez-Lopez

Background: Abdominal obesity (AO) is involved in the development of cardiometabolic disorders, in which factors such as diet and genetics play crucial roles. In this context, interactions between genetic variants and dietary responses may influence metabolic processes associated with AO. Objective: This study aimed to evaluate the effects of a nutrigenetic diet incorporating 21 genetic variants related to lipid metabolism and cardiovascular risk on anthropometric and biochemical parameters and antioxidant capacity in adults with AO. Methods: An eight-week randomized controlled trial was conducted in 58 adults with AO, who were randomly assigned to either a nutrigenetics-guided diet or a standard diet. Participants in the nutrigenetic group underwent genotyping for 21 variants associated with lipid metabolism and cardiometabolic risk in the ABCA1, APOA1, APOA2, APOA5, APOB, APOC3, APOE, CETP, CDKN2B-AS1, CD36, FABP2, FTO, LIPC, LPL, MTTP, MTHFR, NFKB1, PON1, SIRT1, and ZPR1 genes. Anthropometric and biochemical measurements were performed. Antioxidant and oxidative stress biomarkers were measured using colorimetric assays and ELISA, respectively. Results: In baseline-adjusted ANCOVA models controlling for age and sex, with false discovery rate (FDR) correction, both groups achieved comparable reductions in body weight and fat mass under equivalent energy restriction. However, the nutrigenetic group demonstrated significantly greater improvements in insulin levels, HOMA-IR, and high-sensitivity C-reactive protein (hs-CRP) compared with the standard diet group. The nutrigenetic intervention also resulted in greater reductions in the prevalence of elevated TyG index (−20% vs. −10.8%) and HOMA-IR (−33.3% vs. −10.7%), along with a trend toward a greater increase in catalase activity. Conclusions: Compared with a standard dietary intervention, a nutrigenetic diet was associated with greater improvements in fasting insulin, estimated insulin resistance (HOMA-IR), and systemic inflammation (hs-CRP) in adults with AO.

Nutrients doi: 10.3390/nu18213517

Authors: Jung Ho Choi Won Jin Baek Su-Hyun Kim Myoung-Sook Shin

Background/Objectives: Ishige foliacea is an edible brown alga containing bioactive polyphenols with reported neuroprotective properties. Although extracts of I. foliacea have previously been shown to ameliorate cognitive impairment, their effects on pathological tau phosphorylation remain poorly characterized. This study investigated the neuroprotective and cognition-modulating effects of KDC22-01, an aqueous extract of I. foliacea. Methods: KDC22-01 was chemically characterized by total polyphenol and flavonoid-equivalent contents and HPLC fingerprinting. Its effects on pre-aggregated Aβ25–35-induced cytotoxicity and okadaic acid (OA)-induced tau phosphorylation were evaluated in SH-SY5Y cells. Cognitive performance and hippocampal tau phosphorylation were further assessed in male C57BL/6 mice with scopolamine (SCO)-induced cognitive impairment following oral KDC22-01 administration (100 or 300 mg/kg). Results: KDC22-01 protected SH-SY5Y cells against Aβ25–35-induced cytotoxicity, restoring cell viability from approximately 59% to 87% of control levels at 50 μg/mL. KDC22-01 also reduced the OA-induced p-tau (Ser199)/total tau ratio at 25 and 50 μg/mL. In SCO-treated mice, 100 mg/kg KDC22-01 significantly improved performance in the Morris water maze and passive avoidance test, whereas improvements in Y-maze spontaneous alternation did not reach statistical significance. Both KDC22-01 doses reduced hippocampal p-tau (Ser396), while changes in hippocampal Aβ levels were not statistically significant. Conclusions: These findings suggest that attenuation of tau hyperphosphorylation may contribute to the cognitive effects of KDC22-01 and support further investigation of this aqueous I. foliacea extract as a candidate functional-food ingredient for cognitive health.

Nutrients doi: 10.3390/nu18213518

Authors: Vehbi Demircan Kübra Yazar Hakan Eminoğlu Yavuz Katırcılar Abdullah Karakuş Turgay Ulaş Mehmet Sinan Dal Mehmet Orhan Ayyıldız

Background/Objectives: Iron deficiency may be associated with alterations in systemic inflammatory activity and metabolic parameters. However, whether oral and intravenous (IV) iron replacement have different effects on inflammatory markers and serum uric acid remains unclear. We compared inflammatory and metabolic responses to oral and IV iron in premenopausal women with iron deficiency. Methods: This prospective observational study included 72 oral iron recipients, 77 IV iron recipients, and 76 healthy controls. Patients were reassessed at Day 30. The primary outcome was change in C-reactive protein (CRP); changes in erythrocyte sedimentation rate (ESR) and uric acid were secondary outcomes. Additional regressions used robust standard errors, adjusting for age, baseline hemoglobin, and baseline outcome values; the uric acid model additionally included baseline creatinine. Results: Baseline CRP and ESR were significantly higher in both iron-deficient groups than in controls (all Bonferroni-adjusted p < 0.001). The IV iron group had more severe baseline anemia than the oral iron group (median hemoglobin: 8.60 vs. 10.70 g/dL; Bonferroni-adjusted p < 0.001). Increases in hemoglobin, ferritin, and transferrin saturation over 30 days were greater with IV iron (all p < 0.001). Median CRP changes were −0.22 mg/L with IV iron and 0.07 mg/L with oral iron (unadjusted p = 0.041). However, multivariable regression with robust standard errors showed no statistically significant difference in Day 30 CRP after adjustment for age, baseline hemoglobin, and baseline CRP (IV minus oral: −1.585 mg/L; 95% CI, −3.261 to 0.091; p = 0.064; n = 149). The corresponding adjusted analysis showed lower Day 30 ESR with IV iron (−2.118 mm/h; 95% CI, −3.817 to −0.418; p = 0.015; n = 91). The adjusted serum uric acid difference, additionally accounting for baseline creatinine, was not statistically significant (0.389 mg/dL; 95% CI, −0.009 to 0.787; p = 0.055; n = 149). Conclusions: IV iron was associated with greater hematologic and iron-store repletion over 30 days. Adjusted comparisons showed no statistically significant differences in CRP or serum uric acid, whereas ESR was modestly lower with IV iron, with uncertain clinical significance. Nonrandomized treatment allocation and premedication restricted to the IV group preclude attributing these findings solely to iron administration.

Nutrients doi: 10.3390/nu18213516

Authors: Stefano Marelli Alessandro Girombelli Paolo Formenti Francesco Vetrone

Background: Micronutrient abnormalities are frequent in critically ill patients and are associated with organ dysfunction, infection, and adverse outcomes. Yet randomized controlled trials of supplementation have largely failed to demonstrate a consistent mortality or organ-failure benefit. One possible contributor to this translational gap is a systematically under-characterized variable: gut failure. In critical illness, the intestinal barrier is disrupted, epithelial cell mass is depleted, transporter expression is impaired, the intestinal microvasculature exhibits severe dysfunction, and the microbiome undergoes profound dysbiosis. These alterations may collectively impair the absorptive, metabolic, and immunological functions upon which micronutrient homeostasis depends. Purpose: This structured narrative review (SANRA-guided; 202 records) first outlines the epidemiology of micronutrient deficiencies in the ICU and defines gut failure as a biological entity distinct from ileus. It then traces the mechanistic pathways by which a dysfunctional gut disrupts key micronutrients and links this gut–micronutrient axis to immune dysregulation. Overview: We critically appraise landmark ICU supplementation trials and examine whether the absence of gastrointestinal phenotyping, reliance on circulating surrogates of bioavailability, and neglect of microbiome–nutrient interactions may have contributed to heterogeneous or negative findings. Finally, we propose a hypothesis-generating, gut-integrated framework for future studies, comprising gut integrity stratification, microbiome phenotyping, phase-adapted timing and route selection, and microbiome restoration, to realign micronutrient interventions with the biology of the gut–microbiome–immune axis. Direct evidence that gut dysfunction modifies the response to supplementation is lacking.

Nutrients doi: 10.3390/nu18213515

Authors: Mats Kutscher Wendimagegn Alemayehu Nicolò de Biase Julia Benjamins Ryan Vos Marieke C. Haan Cynthia M. Westerhout Justin Ezekowitz Niels Grote Beverborg

Background/Objectives: Iron deficiency (ID) in heart failure (HF) can be classified as low iron storage (LIS) or defective iron utilization (DIU). Whether these phenotypes differ in clinical characteristics, outcomes, and treatment patterns in a real-world decompensated HF population remains unclear. Methods: In this population-based retrospective cohort study, 4818 adults with decompensated HF and available iron indices were classified as LIS (TSAT < 20%, ferritin < 100 µg/L), DIU (TSAT < 20%, ferritin ≥ 100 µg/L), or no ID (TSAT ≥ 20%). All-cause mortality, cardiovascular (CV) hospitalization, HF hospitalization, and initiation of iron therapy were assessed over a median follow-up of 24 months. Outcomes were analyzed using Cox proportional hazards models adjusted for pre-specified covariates, with Fine–Gray competing-risk models for hospitalization and iron therapy initiation, and no ID as the reference group. Results: DIU was present in 30.2% of patients, compared with 38.7% with LIS and 31.1% with no ID. Iron therapy was initiated in 21.5% of patients with DIU compared with 32.0% with LIS, and intravenous (IV) iron in 2.7% versus 4.3%, respectively. After adjustment, DIU was associated with modestly higher CV hospitalization rates (aHR 1.15; 95% CI 1.03–1.28) and with the composite of CV hospitalization or all-cause mortality (aHR 1.09; 95% CI 1.00–1.19), but not with all-cause mortality (aHR 1.03; 95% CI 0.93–1.14) or HF hospitalization (aHR 1.10; 95% CI 0.93–1.27) compared with no ID. LIS was associated with higher risk of HF hospitalization (aHR 1.38; 95% CI 1.19–1.59). Patients with LIS were more likely to initiate iron therapy than those with DIU (adjusted sHR 1.49; 95% CI 1.29–1.71). Conclusions: DIU is a prevalent phenotype of ID in decompensated HF that is less frequently treated with iron than LIS, despite a largely similar prognosis, and is associated with modestly higher CV hospitalization and the composite of CV hospitalization or death, but not independently with mortality. Prospective evaluation of iron replacement strategies, particularly IV iron, in patients with DIU is warranted.

Nutrients doi: 10.3390/nu18213514

Authors: Xiruo Kou Josefa Canals Victoria Arija

Purpose: Early prenatal fatty acid balance is vital for brain development, yet trimester-specific effects on long-term neurodevelopment remain unclear. This study examined associations between maternal omega-6/omega-3 (n-6/n-3) ratios in the first and third trimesters and child neurodevelopment at age four. Methods: In the ECLIPSES cohort (n = 223), maternal serum n-3 and n-6 fatty acids were measured at 12 and 36 gestational weeks. At age four, children’s cognitive and executive function were assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), and the Behavior Rating Inventory of Executive Function (BRIEF)—Preschool Version, respectively. Multivariable regression models were adjusted for sociodemographic and lifestyle factors. Results: A higher n-6/n-3 ratio in the first trimester was significantly associated with poorer executive functioning, as reflected by higher BRIEF scores indicating greater difficulties in inhibition (b = 2.45, p = 0.002), working memory (b = 1.87, p = 0.030), planning/organization (b = 2.20, p = 0.004), and the Global Executive Composite (b = 1.96, p = 0.006). Higher first-trimester ratios were also associated with lower WPPSI working memory performance (b = −2.14, p = 0.013), while general cognitive abilities were largely unaffected. Conclusions: An elevated maternal n-6/n-3 ratio in early pregnancy is associated with poorer executive function in preschool children, whereas evidence linking these ratios to general cognition remains limited. These findings indicate that associations between fatty acid balance and executive function were mainly observed during the first trimester.

Nutrients doi: 10.3390/nu18213513

Authors: Wanyuan Liang Xiang Wang Congyu Sun Yan Chen Ye Sun Dong Wang Jingyi Zhang Chengnan Zhang Bing Wei Junqiang Qiu

Background/Objectives: Evidence is limited on whether carbohydrate formulations enhance resistance training adaptations when protein intake is relatively adequate. This study compared two carbohydrate–protein formulations in healthy young men. Methods: In this randomized, double-blind, placebo-controlled trial, 36 untrained men aged 18–25 years were assigned to a maltodextrin-based carbohydrate control group (PLA), low-molecular-weight carbohydrate plus protein (LMW-CHO+PRO), or high-molecular-weight carbohydrate plus protein (HMW-CHO+PRO). Thirty-three participants completed 8 weeks of supervised resistance training three times weekly and daily supplementation (50 g). Body composition, muscle circumference and thickness, strength, and serum testosterone, cortisol, and testosterone-to-cortisol ratio were assessed before and after intervention. The trial was registered with the Chinese Clinical Trial Registry (ChiCTR2500110509). Results: Body mass, total muscle mass, muscle circumference and thickness, and strength improved in all groups. Both supplementation groups showed greater improvements than PLA across several muscular adaptation measures. Time × group interactions were significant for body mass and total muscle mass, but not fat mass. HMW-CHO+PRO produced greater increases in body mass and total muscle mass than LMW-CHO+PRO; however, no consistent differences between formulations were observed in regional muscle circumference, muscle thickness, strength, or blood biomarkers. Conclusions: Under conditions of relatively adequate protein intake, combined carbohydrate and protein supplementation may provide additional support for resistance training adaptations. These findings do not establish an overall advantage of either formulation, nor can the observed differences be attributed specifically to carbohydrate molecular weight.

Nutrients doi: 10.3390/nu18213512

Authors: Joanna Dragan Ewa Koziorowska-Gawron Marianna Pietkiewicz Anna Pokryszko-Dragan

Due to increasing prevalence and burden of the central nervous system (CNS) disorders and challenges associated with their treatment, there is ongoing search for new therapeutic targets, frequently conducted in the area of natural products. Tea (derived from Camellia sinensis) contains a wide range of bioactive compounds (polyphenols, alkaloids and amino acids) which positively affect general health and function of many systems, including CNS. The aim of this narrative review was to present up-to-date evidence of beneficial effects of tea and its compounds on CNS functions and to outline the most promising perspectives for their utility in management of neurological conditions. Based on extensive literature search, the authors demonstrate biochemical properties of tea-derived substances, molecular mechanisms of their antioxidative, anti-inflammatory and cytoprotective activity, as well as pathways of their specific impact on CNS. The evidence is presented from experimental and clinical studies investigating effects of tea and its compounds on the prevention or amelioration of neurodegenerative disorders (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease), multiple sclerosis, cerebrovascular disease and brain tumors. Finally, limitations and barriers to these investigations are discussed and their emerging future directions are suggested.

Nutrients doi: 10.3390/nu18213511

Authors: Sigrun Chrubasik-Hausmann Julia Vlachojannis

Background/Objectives: Curcumin and Boswellia preparations have been investigated for anti-inflammatory and immunomodulatory effects, but clinical translation is complicated by differences in composition, formulation and exposure. This narrative review examines mechanisms, pharmacokinetics and clinical evidence across immune-mediated, degeneration-associated and acute systemic inflammatory disorders, emphasizing dose comparability. Methods: Literature was identified through iterative PubMed searches and reference list screening, prioritizing recent systematic reviews and meta-analyses and selected primary clinical and pharmacokinetic studies. Experimental pathway effects, human biomarker changes and patient-relevant outcomes were evaluated separately. Results: Clinical findings suggest potential adjunctive symptomatic benefits, with a comparatively larger evidence base in knee osteoarthritis; findings in other indications remain heterogeneous, inconsistent or limited. Differences in active constituents, delivery technology and administered doses restrict comparisons across preparations. Higher systemic exposure does not by itself establish greater clinical efficacy, and neither pharmacokinetic bioequivalence nor clinically equivalent doses have generally been established across formulations. Local gastrointestinal effects and tissue distribution may also contribute to clinical outcomes. Interpretation is further constrained by small trials, overlapping evidence sources and reported industry relationships. Safety considerations include idiosyncratic liver injury associated with turmeric/curcumin products and potential drug interactions. Conclusions: Curcumin and Boswellia preparations show potential as adjunctive interventions, but formulation heterogeneity and limitations of the clinical evidence preclude general assumptions of interchangeability or clinical superiority based on increased bioavailability. Future research should prioritize formulation-specific human pharmacokinetics, dose-finding and adequately powered, independently replicated clinical trials, including direct comparisons where appropriate.

Nutrients doi: 10.3390/nu18213510

Authors: Beata Krasińska Minseung Kang Giuseppe Maria Raffa Calogera Pisano Mariusz Kowalewski Siwon Baek Piotr Suwalski Dagmara Pietkiewicz Szymon Plewa Jan Matysiak Zbigniew Krasiński Julia Frąckowiak Anetta Hanć Tomasz Urbanowicz

Background/Objectives: Sodium–glucose cotransporter-2 inhibitors (SGLT2is) exert metabolic and renal effects extending beyond glycemic control, yet their relationship with circulating trace-element profiles remains poorly characterized. We investigated whether prevalent SGLT2i use was associated with differences in serum trace elements and targeted metabolites, with particular attention to renal function and the possibility of a shared multielement phenotype. Methods: In this exploratory cross-sectional study, serum trace elements and targeted amino acid metabolites were evaluated according to prevalent SGLT2i exposure. The principal clinical comparison comprised participants with diabetes mellitus (DM) receiving SGLT2i (n = 6) versus those not receiving SGLT2i (n = 10). Secondary analyses incorporated the broader three-group cohort. Because of the small exposed group and nonrandom treatment allocation, analyses were considered hypothesis-generating. Group comparisons were complemented by permutation testing, regression adjusted for recalculated uncapped 2021 CKD-EPI estimated glomerular filtration rate (eGFR), false-discovery-rate correction, inter-element correlation analysis, principal-component analysis, and influence diagnostics. Results: Among participants with DM, circulating Cu, Mg, Se, and Zn concentrations were lower in SGLT2i users, with concordant directions across complementary analyses. In the secondary analysis incorporating multiplicity correction across eight molecular outcomes, Cu (q = 0.015) and Se (q = 0.047) met the prespecified FDR threshold, whereas Mg and Zn did not (both q = 0.051). Exploratory principal-component analysis identified a first component explaining 70.8% of the variance across the four measured elements. PC1 was lower among SGLT2i-treated participants and remained associated with exposure after eGFR adjustment (β = −2.43, 95% CI −4.22 to −0.65; p = 0.008); however, this component represents statistical covariance only and should not be interpreted as evidence of a common biological mechanism or shared trace-element depletion. Conclusions: Prevalent SGLT2i use among participants with DM was associated with directionally lower circulating concentrations across several measured trace elements; however, after multiplicity correction, only Cu and Se met the prespecified FDR threshold, whereas Mg and Zn did not. The cross-sectional design, small exposed subgroup, clinical imbalance, and absence of pretreatment, dietary, urinary trace element, inflammatory, treatment duration, and adherence data preclude attribution of this pattern to SGLT2 inhibition. These findings should therefore be considered hypothesis-generating and warrant prospective validation with serial pre- and post-treatment measurements to determine whether the observed phenotype reflects pharmacological effects, treatment selection, the underlying clinical phenotype, or a combination of these factors.

Nutrients doi: 10.3390/nu18213509

Authors: Sandip Mitra Sylwia Żakowska-Biemans

Background/Objectives: Consumer responses to sustainability-relevant food innovations are associated with psychological factors such as food neophobia (FN), food technology neophobia (FTN), trust, perceived risks and benefits, and food-safety-related perceptions. However, these constructs have been examined across heterogeneous contexts, measures, and outcomes. This review aimed to integrate this evidence, examine reported direct and indirect relationships, and develop an evidence-informed conceptual framework. Methods: Five construct-specific searches were conducted in the Web of Science Core Collection and Scopus. Following title/abstract and full-text screening, 288 English-language, peer-reviewed empirical studies with explicit relevance to food-system sustainability were included and synthesised narratively. Results: FN and FTN were generally associated with less favourable consumer responses, although their relative relevance varied with the food, production technology, familiarity, and population. Trust was generally associated with more favourable responses, but associations differed by trust referent and outcome. Innovation-related perceived risk was predominantly associated with less favourable responses, and perceived benefits with more favourable responses. Formal evidence for indirect pathways was limited: only a small number of studies tested FN/FTN- or trust-related indirect relationships through risk and/or benefit perceptions, and their results were heterogeneous. Food-safety-related perceptions, closely related to perceived risk, were operationalised in different ways: safety concerns were generally associated with less favourable responses, whereas perceived safety was associated with more favourable responses. Willingness and behavioural intentions were the most frequently assessed outcomes, whereas few studies assessed behaviour, and evidence from low-income and lower-middle-income countries was limited. Conclusions: Across sustainability-relevant food innovations, consumer responses were generally associated with novelty-related dispositions, referent-specific trust, and parallel risk and benefit appraisals, but the configuration of these relationships varied with the innovation, population, and outcome considered. The evidence is strongest for direct associations with stated responses, whereas indirect pathways and links to behaviour remain less well established. By integrating these constructs within a common framework, this review provides a structured basis for testing their temporal ordering and their relevance to actual purchasing and consumption.

Nutrients doi: 10.3390/nu18213508

Authors: Sthefhany Nohemí Rodríguez-Arellano Jean Pierre González-Gómez José Roberto Aguirre-Sánchez Bruno Gomez-Gil Elisa Barrón-Cabrera Cristobal Chaidez Marcela de Jesús Vergara-Jiménez

Obesity is a complex chronic disease associated with metabolic and inflammatory alterations in which the gut microbiota has emerged as an important contributing factor. Obesity-associated gut dysbiosis involves not only changes in microbial composition but also alterations in microbial functions and metabolites that may affect intestinal barrier integrity, immune regulation, adipose tissue metabolism, insulin sensitivity, and glucose homeostasis. Current microbiota-modulating strategies, including dietary interventions, prebiotics, probiotics, synbiotics, and fecal microbiota transplantation, can influence the gut microbial ecosystem; however, their effects are often highly variable among individuals and generally lack the specificity required to selectively target disease-associated bacterial populations. These limitations have increased interest in precision microbiota modulation, which aims to selectively modify microbial populations, functions, or products while minimizing unnecessary alterations to the remaining microbial community. In this context, bacteriophages represent a promising biological tool because of their ability to specifically target bacterial hosts, offering the possibility of selectively reducing bacterial populations associated with obesity-related metabolic and inflammatory disturbances. Experimental studies and early human trials have shown that bacteriophage-based interventions can modulate gut microbial communities and influence inflammatory responses, supporting their potential relevance to obesity-associated chronic low-grade inflammation. However, no published clinical trials specifically evaluating targeted bacteriophage therapy for obesity treatment were identified, and its efficacy for obesity management remains unestablished. Further research is needed to identify and validate bacterial targets, optimize phage selection and cocktail design, and evaluate phage stability, bacterial resistance, immunomodulatory effects, safety, and host–microbiota interactions before clinical translation can be considered.

Nutrients doi: 10.3390/nu18213507

Authors: Ömer Elma Christopher Long Amber Brown Jamie Dresse Karen Yendole Carol Clark Jonathan Williams Rebecca A. Neal Nils Runge Emma Mosley Sevilay Tümkaya Yılmaz Sumanto Haldar

Background: Fibromyalgia is a chronic pain condition characterised by altered pain processing, widespread pain, and symptoms including sleep disturbance, fatigue, and psychological distress. Emerging evidence suggests that modifiable multimodal lifestyle factors may influence inflammation and pain mechanisms; however, the relationships between multimodal lifestyle factors, systemic inflammatory biomarkers, and pain processing remain poorly understood. In this study we aimed to investigate the associations between lifestyle factors, inflammatory biomarkers, and experimental and clinical pain outcomes in women with fibromyalgia. Methods: Women with fibromyalgia were invited to participate in this exploratory cross-sectional study. Lifestyle factors included diet, perceived stress, sleep, physical activity, heart rate variability, and BMI. Plasma IL-6, IL-10, and TNF-α were measured. Pain outcomes included quantitative sensory testing and patient-reported outcome measures. Spearman’s rank correlations and multiple linear regression analyses adjusted for age and disease duration were performed. Bootstrap 95% confidence intervals were calculated for all estimates, and False Discovery Rate (FDR) corrections using the Benjamini–Hochberg procedure were applied as a sensitivity analysis. Results: Twenty patients were included. Correlation analyses demonstrated that higher perceived stress was strongly associated with greater fibromyalgia impact (r = 0.68, p < 0.001, n = 20), central sensitization (r = 0.67, p < 0.001, n = 20), and current pain intensity (r = 0.64, p = 0.002, n = 20). A more pro-inflammatory diet was positively associated with IL-6 (r = 0.46, p = 0.04, n = 20) and IL-10 (r = 0.47, p = 0.10, n = 13), while higher TNF-α concentrations were associated with lower pressure pain thresholds (overall; r = −0.55, p = 0.021, n = 19; tibialis: r = −0.57, p = 0.010, n = 19). Following adjustment for age and disease duration, associations between stress and fibromyalgia impact, central sensitization, and current and worst pain intensity, together with associations between pro-inflammatory diet and IL-6 and IL-10, and between BMI and IL-10 showed similar directions and effect estimates. However, following FDR adjustment as a sensitivity analysis, no associations retained statistical significance. Conclusions: This study suggests that different modifiable lifestyle factors may be associated with distinct aspects of pain and inflammatory processes in women with fibromyalgia. Perceived stress showed the most consistent associations with pain-related outcomes, while dietary inflammatory potential showed preliminary associations with inflammatory biomarkers that need further investigation.

Nutrients doi: 10.3390/nu18213506

Authors: Silvia Giovannini Alessandra Pedico Anna Maria Malizia Flavia Angelini Giovanna Assante Di Panzillo Claudia Loreti Nadia Morciano Giovanni Frisullo Martina Petrucci Lorenzo Biscotti Federico Biscetti Andrea Flex Letizia Castelli

Post-stroke fatigue (PSF) remains a debilitating barrier to recovery. Chronic inflammation and oxidative stress often create physiological plateaus that standard rehabilitation alone cannot resolve. This single-blind randomized controlled trial (RCT) evaluated the efficacy of Food for Special Medical Purposes formulated with iron and other vitamins and minerals in Sucrosomial® form, allowing improved absorption, bioavailability, and tolerability, as an adjunct to neurorehabilitation. One hundred and twenty stroke patients were randomized into an experimental group (Sid-G) receiving the specific nutraceutical compound or a control group (CG) receiving standard care. Longitudinal assessments from baseline (T0) through 16 weeks (T3) measured clinical outcomes (including fatigue, motor/cognitive function) and physiological markers, specifically phase angle (PhA) derived from Bioimpedance Analysis, and key inflammatory and oxidative stress biomarkers (IL-6 and MPO). The Sid-G cohort demonstrated superior, sustained improvements in fatigue, motor, and cognitive function (p < 0.05). These clinical gains were reflected in the following physiological observations: the time × group interaction for cellular integrity (SPhA) was not significant, though within-group improvements were observed in Sid-G (p = 0.009); at the group level, significant time × group interactions were detected for key inflammatory and oxidative stress markers (IL-6, p = 0.001; MPO, p = 0.026). Correlational analysis revealed a significant association between changes in inflammatory markers and clinical recovery outcomes in Sid-G, a pattern absent in the CG. Adjunctive supplementation may support recovery by helping patients to overcome physiological plateaus. These findings support further evaluation of an integrated, metabolically focused approach to neurorehabilitation.

Nutrients doi: 10.3390/nu18213504

Authors: Lorena Saavedra-Garcia Kiomi Yabiku-Soto Mayra Meza-Hernández Caitlin M. Lowery Donna R. Miles Francisco Diez-Canseco Lindsey Smith Taillie

Background/Objectives: This study aimed to describe changes in children’s dietary intake of selected packaged food and beverage categories that commonly include products high in sugar, sodium, or saturated fat (HFSS packaged products) between 2019 and 2021, in the context of the implementation of Peru’s front-of-package warning label policy. Methods: A longitudinal panel analysis was conducted in four districts of Lima, Peru. Baseline data were collected face-to-face in 2019 and follow-up data by telephone in 2021. Intake was assessed using a semi-quantitative food frequency questionnaire and converted to daily amounts. Energy and nutrient estimates (total sugars, saturated fatty acids, sodium) were derived from product labels corresponding to each study period. Changes between 2019 and 2021 were tested using McNemar tests and quantile regression; analyses were run in Stata v.17. Results: Of 1283 mothers of children aged 3–5 years enrolled at baseline, 1032 completed follow-up (80.4%). Between 2019 and 2021 the prevalence of consumption decreased for some categories, including breakfast cereals and bars (78% to 63%, p < 0.001) and desserts (50% to 32%, p < 0.001), while it increased for others. Median daily energy intake per consumer from food and beverages decreased from 487.3 to 373.2 kcal (p < 0.001). Median total sugar intake decreased from 45.1 to 31.4 g/day, and sodium from 469.4 to 399.4 mg/day (both p < 0.001); saturated fatty acids showed a small decline (8.4 to 7.0 g/day, p < 0.001). Conclusions: Among participating children, estimated energy and nutrient intake from the selected HFSS packaged products declined overall, although changes varied across categories. These findings document temporal changes in the context of FOPWL implementation but cannot isolate the contribution of the policy from other concurrent factors.

Nutrients doi: 10.3390/nu18213505

Authors: Lan Shi Yujia Chen Xiaoxue Wei Xinyi Song Chenjun Wu Fangge Qu Xianqing Tang Daqiao Zhu

Background: Parental misperception of child weight status may influence feeding practices, with implications for early prevention of childhood obesity. This study compared verbal and visual assessments of parental perception and misperception of preschool children’s weight status and examined associations between method-specific parental weight underestimation and feeding practices. Methods: This cross-sectional study included 520 parent–child dyads in Shanghai, China. Parental perception was assessed using a verbal item and visual silhouettes and compared with objectively measured child weight status. Agreement with actual weight status, overall perception patterns, and differences in underestimation between methods were examined using kappa statistics, Bowker’s test, and McNemar’s test, respectively. Associations between method-specific underestimation and feeding practices were examined using multivariable linear regression with false discovery rate (FDR) correction. Results: Agreement with actual weight status was limited for both methods and lower for visual than verbal assessment (quadratic weighted κ = 0.21 vs. 0.37). Underestimation was more common with visual than verbal assessment in the overall sample (45.1% vs. 37.8%, p < 0.001), particularly among children with overweight or obesity (87.5% vs. 43.2%, p < 0.001). Verbal underestimation was associated with lower scores for content-restricted feeding (adjusted β = −0.159, 95% CI: −0.312 to −0.005, p = 0.043) and behavior-restricted feeding (adjusted β = −0.129, 95% CI: −0.252 to −0.007, p = 0.038), whereas visual underestimation was not consistently associated with feeding practices. However, neither verbal association remained statistically significant after FDR correction (both adjusted p = 0.203). Conclusions: Verbal and visual assessments showed different patterns of parental weight perception and misperception and different associations between parental underestimation and feeding practices. Appropriate tool selection may support parental recognition of children’s weight status and feeding-related guidance for early prevention of childhood obesity.

Nutrients doi: 10.3390/nu18213503

Authors: Antonio Peña-Fernández Tomás Cámara-Pastor M. Ángeles Peña Fernández

Background/Objectives: Whole-diet patterns in geographically diverse university populations remain insufficiently characterised. We examined food-group consumption and dietary patterns according to sex and geographical background in a historical UK university cohort. Methods: This cross-sectional analysis included 111 students assessed at De Montfort University, Leicester, in early 2016. Habitual intake was assessed using an expanded, adapted EPIC-Norfolk food-frequency questionnaire. Fifteen food groups were evaluated using principal component analysis after log1p transformation and standardisation; between-group comparisons were adjusted for relevant covariates and subjected to Benjamini–Hochberg false-discovery-rate correction. Results: The participants had a mean age of 20.4 ± 1.2 years, and 70.3% were female. Three patterns—Plant-rich, Animal-source foods, and Energy-dense/discretionary—explained 46.25% of the variance, compared with 35.24% for the two-component alternative. Parallel analysis supported retention of three components; bootstrap results favoured their overall reproducibility but indicated substantial uncertainty in individual food-group loadings. Males had lower adjusted Plant-rich scores than females (−0.43 SD, 95% CI −0.76 to −0.10; q = 0.04). Plant-rich and Animal-source foods scores differed by geographical background (q = 0.006 for both global tests), whereas the Energy-dense/discretionary pattern did not. Conclusions: These exploratory patterns characterise dietary heterogeneity in this historical cohort but require replication in larger, contemporary samples.

Nutrients doi: 10.3390/nu18213502

Authors: Cyntia Carolina García-Ramírez Fabiola Martín-del Campo José Efrén Ortíz-González Tonatiuh González-Heredia Alfonso M. Cueto-Manzano

Chronic kidney disease (CKD) is a serious public health issue affecting 10% of the global population. CKD is associated with intestinal dysbiosis, characterized by a reduction in saccharolytic bacteria and an increase in proteolytic genera that produce uremic toxins. This may promote intestinal barrier impairment (“leaky gut” syndrome), chronic low-grade inflammation, and protein-energy wasting (PEW), although most of the supporting evidence is observational. Kidney transplantation (KT) improves survival but may not fully reverse dysbiosis. KT recipients are exposed to residual uremia, use of perioperative antibiotics, and chronic immunosuppressive regimens. Drugs such as mycophenolate mofetil can cause gastrointestinal toxicity and reduced intake due to diarrhea or enteropathy, whereas corticosteroids and calcineurin inhibitors induce hyperphagia, hypomagnesemia, and insulin resistance. These factors may lead to a spectrum of complications ranging from persistent PEW in the early post-transplant period to a higher prevalence of weight gain and obesity, sarcopenia, and post-transplant diabetes. Furthermore, the microbiota may modulate pharmacological responses; in experimental and small clinical studies, genera such as Faecalibacterium have been linked to alterations in the metabolism of tacrolimus, potentially altering its therapeutic levels and the risk of nephrotoxicity or rejection. Interventions using biotics (prebiotics, probiotics, and synbiotics) are emerging as a potential adjuvant strategy to restore eubiosis and mitigate PEW. In non-dialysis and dialysis CKD patients, some biotics have been reported to reduce uremic toxins and inflammatory cytokines (IL-6, TNF-α), although results are heterogeneous. However, there is no evidence available regarding its ability to improve nutritional status following a KT. Safety data are limited, although biotic interventions are generally considered safe. Future prospective studies are required to confirm their efficacy and immunological safety, as well as any possible association with infectious adverse events.

Nutrients doi: 10.3390/nu18213501

Authors: Doh Hoon Chung Jiwon Baek Sung Pyo Park Sean Hyungwoo Kim Donghyun Jee

Background/Objectives: Experimental studies implicate the gut microbiome in diabetic retinopathy (DR), but population-based data on probiotic supplementation and DR are lacking. We examined this association in Korean adults with diabetes. Methods: We analyzed 2071 adults with diabetes in the Korea National Health and Nutrition Examination Survey 2018–2021 with graded fundus photographs and a product-level dietary supplement interview. We used survey-weighted logistic regression (prespecified) and Poisson regression (added after the initial analysis) estimated odds ratios (ORs) and prevalence ratios (PRs), adjusted for age, sex, hypertension, smoking, and household income (Model 1), and additionally for diabetes duration and glycated hemoglobin (HbA1c) (Model 2, primary), with further adjustment for clinical, lifestyle, and dietary factors. Results: Probiotic supplements were used by 10.4% of participants. Weighted DR prevalence was 11.0% among users and 21.1% among non-users (Model 2 PR 0.57, 95% CI 0.36–0.90; OR 0.49, 95% CI 0.28–0.86; 27 exposed cases; fully adjusted PR 0.59, 95% CI 0.37–0.95). In exploratory analyses, compared with non-use, the PRs were 0.76 (95% CI 0.45–1.29; not statistically significant) for use of <1 year and 0.28 (95% CI 0.13–0.62) for use of ≥1 year. No probiotic user had vision-threatening DR, compared with 3.9% of non-users (unadjusted design-based p = 0.024), a descriptive observation that does not demonstrate a protective effect. Use of any non-probiotic supplement was not associated with DR (PR 0.92), although vitamin C and vitamin A/lutein supplements showed inverse associations of similar magnitude. Conclusions: Probiotic supplement use was associated with a lower prevalence of DR among Korean adults with diabetes. These cross-sectional findings are consistent with, but do not establish, a role of the gut–retina axis in DR and require confirmation in prospective studies.

Nutrients doi: 10.3390/nu18213500

Authors: Cristina Sánchez-Quesada

Chronic non-communicable diseases remain the leading source of morbidity and mortality in ageing populations, and diet is one of the few modifiable determinants shared by most of them [...]

Nutrients doi: 10.3390/nu18213499

Authors: Zhenxia Li Can Xu Qingjing Liao Fayin Ye Fasheng Lv Cai Peng Zhenyu Chen Lin Lei

Background: Radish red anthocyanins (RRA) extract, derived from geographical-indication Yanzhi radish from Fuling, Chongqing, China, was investigated to attenuate high-fat diet- induced aging in Drosophila melanogaster. RRA extract, rich in acylated pelargonidin- and cyanidin-based anthocyanins, extended lifespan without reducing food intake, improved reproductive and locomotor performance, raised superoxide dismutase and catalase activities, whereas reduced malondialdehyde accumulation. Mthoths: Using a Drosophila melanogaster model, we investigated the anti-aging effects of RRA extract and its potential underlying mechanisms. Results: It enhanced resistance to starvation, cold, and heat stress, reduced age-associated intestinal leakage, and regulated antioxidant- and autophagy-related genes, particularly manganese superoxide dismutase (SOD2) and autophagy-related 8a (Atg8a). Gut microbiota analysis showed high-dose RRA supplementation selectively increased Pseudomonas-related amplicon sequence variants 30 and 31. Untargeted metabolomics showed variations in glycerophospholipid, sphingolipid, nucleotide, and amino acid metabolism. Correlation results linked these Pseudomonas-related bacteria with lipid/nucleotide-related metabolites and stress resistance. Conclusions: RRA extract alleviated diet-induced aging through antioxidant defense, intestinal protection, and gut microbiota–metabolite modulation, providing a research basis for high-value utilization of Yanzhi radish anthocyanins.

Nutrients doi: 10.3390/nu18213498

Authors: Laurence Claes Dirk Smits Lore Vankerckhoven Glenn Kiekens Koen Luyckx

Background/Objectives: Avoidant/Restrictive Food Intake Disorder (ARFID) is characterized by restricted food intake with significant physical and/or psychosocial consequences. ARFID comprises three subtypes: sensory-based food avoidance, lack of interest in eating, and fear of aversive consequences of eating. The Nine Item ARFID Screen (NIAS) was developed to assess these three ARFID subtypes. This study evaluated the psychometric properties of the Dutch NIAS in a Flemish adult sample. Methods: A community sample of 424 adults (18–65 years) completed the Dutch NIAS and self-report measures assessing eating disorder symptoms, psychological symptoms, and identity functioning. The factor structure, internal consistency, and measurement invariance of the NIAS scales were examined, as were the associations between the NIAS scales and psychological symptoms. Results: Confirmatory factor analysis supported the three-factor structure of the Dutch NIAS. The three subscales showed good internal consistency (all α/ω ≥ 0.82). Partial scalar invariance across BMI categories was supported after freeing Item 7, whereas scalar invariance across gender and age groups was not established. NIAS subscale scores were significantly positively related to eating disorder symptomatology, anxiety, depression, somatic symptoms, and identity diffusion, and they were negatively associated with BMI, identity synthesis, and self-esteem. Conclusions: The Dutch NIAS demonstrates good reliability and factorial validity for assessing ARFID-related symptoms in the younger adult subgroup (<40 years) across gender and weight categories. However, the observed differences in measurement invariance, particularly across age groups, warrant further investigation in larger and more diverse samples.

Nutrients doi: 10.3390/nu18213497

Authors: Rossana Iannitti Giada Ceccarelli Valentina Melfi Mariano Licciardi Francesco Montalbano Desirée Bartolini Elisa Menicali Alice Coletti Chiara Pennetta

Background/Objectives: Salvia officinalis L. is widely used in food supplements, particularly those intended to support women’s health and alleviate menopausal vasomotor symptoms. However, the extent to which estrogen receptor signaling contributes to its reported clinical benefits remains unclear. Therefore, evaluating its potential endocrine activity is a key aspect of its toxicological characterization and overall safety assessment. The present study aimed to investigate the potential estrogenic effects of a standardized Italian Salvia officinalis L. extract (Salvira™), as well as its biological effects on estrogen-responsive breast cancer cells (MCF-7). Methods: In vitro enzymatic assays and estrogen receptor alpha (ERα) agonist- and antagonist-mode experiments were performed to assess its ability to modulate ERα signaling. Moreover, cell viability, proliferation, and clonogenic capacity were assessed in MCF-7 cells following exposure to increasing concentrations of the extract. Results: The extract did not exhibit estrogenic activity in all experimental dose–response assays. In MCF-7 cells, treatment with the sage extract did not produce an overall effect on cell viability or proliferative capacity. Moreover, no impairment of long-term clonogenic potential was observed at the tested concentrations. Conclusions: Under the experimental conditions investigated, the present findings suggest that the standardized Salvia officinalis L. extract showed no evidence of estrogenic activity and did not induce relevant ERα-mediated biological effects in estrogen-responsive MCF-7 cells. These findings contribute to the characterization of the endocrine safety profile of the extract, supporting its safe use as an ingredient in food supplements.

Nutrients doi: 10.3390/nu18213496

Authors: Kyung-Hyun Cho Yeong-Bae Lee Min Ju Kang Dhananjay Yadav

Objectives: Early non-pharmacological interventions for people with subjective memory decline (SMD) are increasingly advocated in preventing age-related cognitive decline and potentially delaying progression to mild cognitive impairment or dementia. In this multicenter clinical trial (RAYDELP1), we evaluated the efficacy and safety of sugarcane-derived Cuban policosanol (PCO) on cognitive function, superoxide dismutase (SOD) activity, inflammatory markers, and metabolic panels in adults aged 55–85 years with subjective cognitive complaints. Methods: A 12-week, randomized, double-blinded, placebo-controlled trial was conducted at Gachon University Gil Medical Center and Seoul Veterans Hospital in adults with SMD complaints. Individuals were randomized equally into three groups: placebo, PCO 20 mg group, or PCO 40 mg group. Assessment of cognitive function was performed using the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog 11) and the Korean Mini-Mental State Examination (K-MMSE). All measurements, including SOD activity, inflammatory markers, and metabolic parameters, were analyzed in blood samples at baseline and after 12 weeks. For an exploratory subgroup analysis, participants receiving statins and those with potential ceiling effects or greater cognitive impairment based on K-MMSE scores were excluded. The K-MMSE range of 18–26 was used as an exploratory criterion to reduce heterogeneity in baseline cognitive scores, resulting in a refined analysis population of 56 participants. Results: In the refined SMD population, SOD activity increased significantly in the PCO 40 mg group after 12 weeks (mean change, +0.16 ± 0.25 U/mL; p = 0.0109) with increasing HDL-C, whereas changes in the placebo groups were not statistically significant (+0.08 ± 0.24 U/mL, p = 0.1873) with decreasing HDL-C. HDL-C levels increased in a dose-dependent manner in both the PCO 20 mg (+0.78 ± 5.1 mg/dL) and PCO 40 mg (+2.2 ± 6.7 mg/dL) groups within and between the groups. Both PCO groups showed significant differences compared with placebo in the between-group analysis and baseline-adjusted ANCOVA (p = 0.0124 and p = 0.0142, respectively). K-MMSE place-orientation scores improved significantly from baseline within both PCO groups (20 mg: 0.94 ± 0.87, p = 0.0003; 40 mg: 0.47 ± 0.77, p = 0.0155), whereas no significant within-group change was observed in the placebo group. Similarly, ADAS-Cog 11 language scores improved significantly within both PCO groups (20 mg: −1.17 ± 1.92, p = 0.0194; 40 mg: −0.95 ± 1.58, p = 0.0176). The 20 mg PCO group also showed a significant within-group decrease in Visual CPT false-alarm errors (−3.83 ± 7.13, p = 0.0357). However, between-group comparisons and baseline-adjusted ANCOVA did not demonstrate statistically significant differences in the selected cognitive outcomes. Conclusions: In the analyzed study population, HDL-C levels increased numerically in both PCO groups in a dose-dependent manner. The PCO 40 mg group showed a significant within-group increase in serum SOD activity, while improvements in selected cognitive domains were observed within both 20 mg and 40 mg PCO groups. However, no significant differences were found in between-group or ANCOVA analyses. PCO was well tolerated, and further clinical studies are warranted to confirm these exploratory findings and clarify its potential effects on cognitive function and enhancement of HDL quantity and quality.

Nutrients doi: 10.3390/nu18213495

Authors: Yetong Ma Mengke Zhang Xin Qin Xinsheng Zhang Lu Liu Yinghua Liu

Background/Objectives: Questionnaires regarding intake and routine lipid panels do not indicate fatty-acid composition. Dried blood spot (DBS) whole-blood profiling is a minimally invasive complement not yet linked to a vascular structural endpoint. We tested whether DBS composition tracks carotid wall burden in Chinese adults with metabolic-risk features and established carotid structural involvement using a prespecified panel and compositional analysis. Methods: Fasting DBS gas chromatography resolved 37 fatty acids in 230 adults (47.4% men) meeting a prespecified maximum carotid wall thickness (max-CWT) ≥ 1.0 mm eligibility criterion. A total of 16 prespecified measures were modelled against ln(max-CWT) with multivariable adjustment and Benjamini–Hochberg correction pooled across 16 tests; the 26-part composition was examined by isometric log-ratio (ILR) analysis. Results: Under pooled false-discovery-rate control, α-linolenic acid (ALA) and linoleic acid (LA) were inversely and oleic acid positively associated with max-CWT (per 1-SD β = −0.063, −0.068 and 0.080; all q < 0.05). The full composition was associated (F(25,196) = 2.26, p = 0.0011), whereas EPA and the AA/EPA ratio remained weaker, family-level signals. Conclusions: To our knowledge, this is the first dual-route DBS compositional analysis linked to a structural vascular endpoint, and it identified a candidate nutritional–metabolic pattern—lower ALA and LA and higher oleic acid—linked to wall thickness in adults with established structural involvement. This pattern warrants prospective investigation and does not by itself support any dietary recommendation.

Nutrients doi: 10.3390/nu18213494

Authors: Mi-Sun Lee Kazimierz Wilkoszewski Natalia Ziółkowska Soo-Young Bhang Kamilla Bargiel-Matusiewicz

Objectives: Pediatric eating behavior and psychological adjustment may be related to family food-related attitudes. This cross-sectional study examined associations between parental and child food neophobia (FN) in South Korean parent–child dyads and evaluated whether child FN statistically mediated associations between parental FN and child eating-behavior and psychological-symptom indicators. Methods: A cross-sectional study was conducted on a sample of 300 parent–child dyads aged 6–12 years recruited through community mental health and counseling centers. Parent-reported FN, CEBQ indicators, and PSC-17 symptoms were analyzed using multivariable linear regression and 5000-resample bias-corrected bootstrap mediation models. Results: Parental FN was positively associated with parent-reported child FN (B = 0.31, 95% CI 0.21–0.42). In the mutually adjusted PSC-17 model, parental FN (B = 1.09, 95% CI 0.26–1.93) and child FN (B = 0.80, 95% CI −0.02–1.62) showed positive associations with PSC-17 Total; the child-FN association was not conventionally statistically significant (p = 0.056). The bootstrap indirect association through child FN was B = 0.212 (95% bias-corrected bootstrap CI 0.015–0.468). For the exploratory CEBQ Total, the corresponding indirect association was B = −0.706 (95% bias-corrected bootstrap CI −1.142 to −0.334). Conclusions: The findings indicate cross-sectional associations and statistically detectable indirect associations, but they do not establish temporal transmission or causality. Longitudinal and intervention studies are needed to determine whether these patterns are reproducible and temporally ordered.

Nutrients doi: 10.3390/nu18213493

Authors: Paweł Bryła Beata Ciabiada-Bryła

Background/Objectives: This study compared the opinions of nutrition professionals from Poland, France, the United Kingdom, and Germany regarding the perceived importance and perceived use of policy instruments, audience characteristics affecting policy effectiveness, and credibility of nutrition information sources. Methods: A cross-sectional survey was completed by 131 nutrition professionals (56 Poland, 36 France, 26 UK, 13 Germany), who rated 14 policy instruments, 11 audience characteristics, and 9 information sources. Data were analyzed using ANOVA, ANCOVA, post-hoc tests with Bonferroni correction, and analysis of open-ended responses. Results: Across policy instruments, perceived importance consistently exceeded perceived use, most strongly for nutrition education for children/adolescents (4.59 vs. 2.76, p < 0.001), information on product processing (3.92 vs. 2.44), dietitian recommendations (3.86 vs. 2.94), higher taxes on less healthy foods (3.46 vs. 2.50), and social marketing (3.60 vs. 3.19). After Benjamini–Hochberg correction, in ANCOVAs adjusted for age and professional experience, cross-national differences were observed in the assessment of credibility for health claims, nutrition claims, social marketing campaigns, cooking blogs, and nutrition apps. Qualitative findings emphasized the need for compulsory school-based nutrition education, better access to qualified professionals, and stricter regulation of food marketing and labelling. Conclusions: Nutrition professionals perceive a clear underutilization of key policy instruments, particularly educational and fiscal measures. Greater involvement of dietitians in context-sensitive policy design and implementation is recommended to bridge the gap between policy intentions and real-world effectiveness.

Nutrients doi: 10.3390/nu18213492

Authors: Neslişah Rakıcıoğlu Rüveyda Esra Özkalaycı Canan Altınsoy Çağlayan Keklikkıran Eda Kaya Yusuf Yılmaz

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and linked to shift work. This study aimed to investigate the associations of circadian rhythm, sleep characteristics, anthropometric measures, and adiposity-related parameters with controlled attenuation parameter (CAP) values, and to assess their independent associations and sex-specific discriminatory performance in identifying hepatic steatosis among shift and non-shift workers. Methods: A total of 436 workers (328 men and 108 women), aged 19–64 years, from seven large-scale tea factories in Rize, Türkiye, were included. Social jetlag (SJL) and eating jetlag (EJL) were calculated from workday–free-day differences in sleep and meal timing, respectively, and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Multivariable linear regression and sex-specific receiver operating characteristic analyses were performed. Results: Mean SJL (p = 0.017) and the distribution of SJL categories (p = 0.022) differed significantly between female shift and non-shift workers, whereas neither differed in men (p = 0.827 and p = 0.542, respectively). These comparisons are exploratory because SJL and EJL estimates are not directly comparable across rotating shift assignments or between shift and non-shift workers. CAP values and the prevalence of CAP-defined hepatic steatosis did not differ significantly by shift-work status in either sex. CAP was positively correlated with anthropometric and adiposity-related measures, with the strongest adjusted correlations observed for waist circumference, abdominal volume index (AVI), BMI, and body fat mass (all rs = 0.66, p < 0.001). In the fully adjusted regression model, age, BMI, and neck circumference were independently associated with higher CAP values, whereas SJL, EJL, sleep duration, and PSQI total score were not. In sex-specific ROC analyses, waist circumference and AVI showed the highest discriminatory performance in men (both AUC = 0.86), whereas BMI showed the highest discriminatory performance in women (AUC = 0.81). SJL and EJL did not significantly discriminate hepatic steatosis in either sex, while sleep duration showed weak discrimination in women (AUC = 0.63, q = 0.042). Conclusions: Anthropometric and adiposity-related measures were strongly associated with CAP values and showed good sex-specific discriminatory performance for hepatic steatosis. However, SJL findings, particularly comparisons by shift-work status, should be considered exploratory given the limited comparability of SJL and EJL estimates among rotating shift workers and between shift and non-shift workers. These simple, readily obtainable anthropometric measurements and derived adiposity indices may facilitate preliminary risk stratification for hepatic steatosis in occupational settings.

Nutrients doi: 10.3390/nu18213491

Authors: Patrick Haselwanter Max Oberweger Sarah Schwaiger Marlene Hintersteininger Marlene Riedl-Wewalka Mathias Maleczek Daniel Laxar Martina Hermann Nina Buchtele Thomas Staudinger Christian Zauner Mathias Schneeweiss-Gleixner

Background/Objectives: Refeeding syndrome (RFS) is a potentially life-threatening complication of nutritional support in critically ill patients. Its incidence and clinical relevance in patients requiring extracorporeal membrane oxygenation (ECMO) are unknown. We retrospectively investigated the incidence, characteristics and clinical relevance of RFS in COVID-19 patients receiving venovenous (vv-)ECMO support. Methods: In a secondary analysis of 101 COVID-19 patients treated with vv-ECMO at a tertiary center, RFS was defined by a decrease of more than 0.16 mmol/L in serum phosphate to a value below 0.65 mmol/L within seven days of starting medical nutrition therapy (MNT), or a pre-existing phosphate below 0.65 mmol/L. Electrolyte trajectories, nutritional delivery, predictors of RFS, and the association with ICU mortality were analyzed. Robustness was assessed across alternative published definitions. Results: RFS developed in 46 of 101 patients (45.5%), with an incidence ranging from 23.8% to 84.2% depending on the definition applied. Patients with RFS had a lower body mass index and required significantly more phosphate substitution than those without (93.5% vs. 43.6%; p < 0.001). Early energy delivery did not differ between groups and was not associated with RFS. RFS was not associated with ICU mortality (41.3% vs. 41.8%; adjusted hazard ratio 0.80, p = 0.51), a finding consistent across all definitions examined. Conclusions: In this COVID-19 vv-ECMO cohort, refeeding-associated hypophosphatemia was frequent but not associated with caloric delivery or ICU mortality under close electrolyte monitoring. These hypothesis-generating findings do not support reducing caloric intake for isolated hypophosphatemia and require prospective confirmation.

Nutrients doi: 10.3390/nu18213489

Authors: Litao Du Lina Wang Ke Chen Qiang He Yang Pan Xianliang Zhang Si Chen

Objectives: This study aimed to identify rest–activity rhythm (RAR) phenotypes and examine the independent and joint associations of RAR phenotypes and diet quality with frailty among rural older adults. Methods: This cross-sectional study included 1203 rural Chinese adults aged 65 to 85 years. Accelerometer-derived inter-daily stability, intra-daily variability, and relative amplitude were used to identify RAR phenotypes through latent profile analysis. Diet quality was assessed using the China Prime Diet Quality Score, and frailty was assessed using the Fried Frailty Phenotype. RAR phenotypes and median-dichotomized diet quality were combined into joint groups. Robust linear and ordered logistic regression examined associations with frailty score and severity, respectively. Subgroup and interaction analyses were conducted by sex and age group. Results: Five RAR phenotypes were identified. Compared with the robust-rhythm phenotype, the severely disrupted phenotype was associated with a 0.516-point higher frailty score and 148.6% higher odds of greater frailty severity, while the fragmented low-amplitude phenotype was associated with 49.3% higher odds. Each 10-point increase in diet quality score was associated with a 0.127-point lower frailty score and 29.3% lower odds of greater frailty severity. Joint analyses showed greater frailty in both typical-rhythm and fragmented low-amplitude phenotypes combined with lower diet quality (β = 0.229, OR = 2.020; β = 0.250, OR = 2.179, respectively), with the highest frailty score observed in the severely disrupted and lower-diet-quality group (β = 0.600; OR = 2.774). Severely disrupted combinations were associated with greater frailty whether diet quality was higher (β = 0.512; OR = 3.092) or lower (β = 0.600; OR = 2.774). No evidence of overall interaction by sex or age group was observed. Conclusions: Better diet quality and more robust RAR patterns were independently associated with lower frailty. Considering both factors may provide a broader perspective on behavioral factors related to frailty in older adults.

Nutrients doi: 10.3390/nu18213490

Authors: Tomonari Abe Nick Yoshida Mohamed Abdelhakim Hiroshi Abe

Background: Nutritional strategies targeting NAD+ metabolism, mitochondrial function, and metabolic resilience are gaining attention as potential approaches to healthy aging. This study investigated the short-term physiological, cognitive, and aging-related responses to NMN-based nutritional formulations, including combinations with β-hydroxybutyrate, ginsenosides, and complementary metabolic modulators. Methods: In this 42-day, open-label, four-arm exploratory clinical study, 40 Japanese adults aged 45–65 years were included in the final analysis: placebo (n = 10), NMN alone (n = 9), a core combination (n = 10), and an expanded eight-component formulation (n = 11). Cardiopulmonary exercise testing (CPET) and computerized cognitive assessments (CogniTrax) were performed at baseline and week 6. Additional exploratory analyses evaluated immune and inflammatory biomarkers and model-derived functional-age estimates in a placebo-versus-expanded-formulation subset. DNA methylation and transcriptomic profiles were independently assessed in a separate eight-participant pilot. Results: The intervention was associated with high recorded adherence and no reported serious adverse events. Although between-group comparisons did not demonstrate statistically significant improvements in the selected cardiopulmonary or cognitive outcomes, several cognitive measures showed favorable descriptive changes in the expanded-formulation group relative to placebo, including the Neurocognitive Index (+3.09 vs. −1.90), composite memory (+5.82 vs. −5.30), and verbal memory (+9.00 vs. −2.50). Exploratory biomarker analyses identified nominal between-group differences in CTACK (p = 0.015) and GDF-15 (p = 0.022), without adjustment for multiple testing; the direction of these changes does not establish clinical benefit. A model-derived functional-age composite decreased by 2.79 years in the expanded-formulation group compared with 0.63 years in placebo. In the separate uncontrolled molecular pilot, DNAm PhenoAge relative to chronological age decreased by approximately 4.1 years, accompanied by nominal transcriptomic changes. These exploratory age-related measures do not establish biological age reversal. Conclusions: This exploratory study demonstrates the feasibility of short-term administration of NMN-based multi-ingredient nutritional formulations and provides multidomain descriptive observations across cognitive, physiological, inflammatory, and molecular measures. While the findings do not establish clinical efficacy or ingredient-specific effects, they offer a foundation for hypothesis development and the design of larger, randomized, double-blind trials with prespecified outcomes.

Nutrients doi: 10.3390/nu18213488

Authors: Vittorio Schweiger Barbara Ganz Erica Secchettin Marta Nizzero Luca Polati Alessandro Picelli Giustino Varrassi Luca Dalle Carbonare Leonardo Gottin Alvise Martini Enrico Polati

Chronic pain (CP) is a major cause of disability worldwide and reflects interactions among multiple pathophysiological mechanisms. Despite the availability of pharmacological therapies, many patients continue to experience inadequate pain control, supporting interest in complementary approaches. Nutraceuticals have been investigated as potential adjuncts because several compounds modulate biological pathways implicated in pain persistence. This narrative review provides a mechanism-based overview of nutraceuticals in CP across five interconnected domains: neuroinflammation, oxidative stress and mitochondrial dysfunction, central sensitization, peripheral sensitization, and descending inhibitory modulation. Literature was identified in PubMed/MEDLINE and the Cochrane Library, with the final update completed on 8 October 2026; preclinical mechanisms and clinical efficacy were evaluated separately. Earlier short-term trials of alpha-lipoic acid suggested symptomatic improvement in diabetic peripheral neuropathy, whereas a 2024 Cochrane review found little or no benefit after six months. Evidence syntheses suggest possible analgesic effects of palmitoylethanolamide in mixed chronic pain populations and of curcuminoids in knee osteoarthritis. Clinical studies of omega-3 fatty acids also suggest a possible reduction in pain intensity, although substantial heterogeneity across conditions, formulations, and study designs limits interpretation. Across compounds, mechanistic plausibility generally exceeds evidence of clinical efficacy and direct target engagement in humans. Future studies should prioritize standardized formulations, clinically relevant outcomes, adequate follow-up, safety assessment, and mechanistic biomarkers within phenotype-informed pain management.

Nutrients doi: 10.3390/nu18213487

Authors: Xi Liang Tianhu Shan Jianhao Gao Haichao Wen Jiawen Wang Zhe Zhang Huaqi Zhang Hui Liang

Objectives: This study explored whether the combined administration of niacin and B. animalis subsp. lactis F1-7 exerts a protective effect against alcohol-induced liver injury via the gut-liver axis, with a specific focus on the HCAR2-NLRP3 signaling pathway, and further investigated the functional roles of gut microbiota and metabolites. Methods: A mouse model of alcoholic fatty liver disease was established via chronic ethanol feeding with the Lieber–DeCarli liquid diet. Experimental animals were divided into six intervention groups: control group, model group, niacin alone, F1-7 alone, combined niacin and F1-7 (NF), and antibiotic pretreatment followed by NF intervention. Results: The NF intervention significantly improved serum lipids, reduced ALT/AST, alleviated hepatic steatosis and inflammation, and restored intestinal barrier integrity, while upregulating HCAR2 and suppressing NLRP3 activation; these effects were largely abolished by antibiotics. The 16S rRNA sequencing revealed that NF intervention reshaped the gut microbiota, enriching beneficial genera such as Lactobacillus, Bifidobacterium, and Faecalibaculum. Untargeted metabolomics showed that NF intervention enriched the ketone body β-hydroxybutyrate, which was positively correlated with the abundance of beneficial bacteria; this metabolite was identified as a key node in the ketone-body synthesis/degradation pathway and ranked among the top differential metabolites by VIP score. Conclusions: The combination additively alleviates alcohol-induced hepatic and intestinal injury in a gut microbiota-dependent manner. Intestinal β-hydroxybutyrate was enriched following the combined intervention in a microbiota-dependent fashion, and this enrichment was associated with HCAR2 activation and NLRP3 inhibition. These findings demonstrate that the protective action is largely dependent on an intact gut microbiota and support the combined intervention as a promising strategy against alcoholic liver disease.

Nutrients doi: 10.3390/nu18213486

Authors: Salvatore Saccone Francesca Bruno Desiree Brancato Elvira Coniglio Valentina Sturiale Concetta Federico

Nutrigenetics and nutrigenomics represent complementary dimensions of the complex relationship between diet and the human genome and provide a conceptual basis for precision nutrition. Nutrigenetics investigates how interindividual genetic variability influences food perception, dietary behavior, nutrient metabolism, and biological responses, whereas nutrigenomics explores how nutrients and bioactive food components modulate gene expression, signaling pathways, and epigenetic mechanisms. Importantly, these processes are interconnected: genetic variation may influence dietary exposure itself through effects on sensory perception, food preferences, appetite, and eating behavior, while additional genetic differences can modify nutrient absorption, metabolism, bioavailability, and downstream molecular responses. This review integrates these interactions within a diet–genome–phenotype framework, incorporating nutrient-responsive molecular pathways, epigenetic regulation, and the gut microbiota as additional determinants of interindividual variability. Overweight and obesity are examined as a paradigmatic application of this framework, illustrating how genetic determinants of dietary exposure and metabolic response may jointly contribute to susceptibility and heterogeneous responses to nutritional interventions. We further propose a research-oriented Weighted Evidence Score (WES) for the evidence-based prioritization of candidate genetic variants, integrating seven domains of functional evidence, phenotypic evidence, independent replication, genotype–diet interactions, nutritional intervention evidence, incremental predictive value, and population validity. In a pilot application to twelve illustrative variants or haplotypes, eight were classified as Tier 2 and four as Tier 3, with none meeting the requirements for Tier 1. Rather than representing an immediately actionable clinical test, such a research-oriented panel is intended as a dynamic hypothesis-generating and validation tool integrating genotype with dietary exposure, metabolic and molecular biomarkers, lifestyle factors, and phenotypic outcomes. Particular emphasis is placed on distinguishing evidence-based research prioritization from the additional validation required for clinical actionability. Finally, ethical, professional, and social challenges related to genomic information, including informed consent, privacy, communication, population diversity, and equitable implementation, are considered. Precision nutrition should ultimately be defined not by the amount of molecular information collected, but by its demonstrated ability to provide incremental predictive value and improve nutritional interventions beyond what can be achieved using established clinical, dietary, and population-based approaches.

Nutrients doi: 10.3390/nu18213485

Authors: Manuela Chiavarini Jacopo Dolcini Giorgio Firmani Pamela Barbadoro

Background: Associations between diet and asthma in adults remain uncertain. Objective: To examine associations between two exploratory food-frequency scores and self-reported asthma. Methods: We analysed public-use data from the 2023 Italian Aspects of Daily Life survey. The PRO and ANTI scores summarised selected food frequencies; neither was a validated measure of dietary inflammatory potential. Survey-weighted logistic models were adjusted for age group, sex, education, body mass index, smoking, and household economic resources. Continuous and tertile specifications were fitted separately; an additional model included both continuous scores. Results: Among 33,182 adults with asthma information, weighted prevalence was 4.62% (95% CI 4.37–4.89). The regression sample included 32,000 adults and 1460 asthma cases. In the mutually adjusted model, PRO was not associated with asthma (OR per 10 points 1.004, 95% CI 0.952–1.059), whereas ANTI was inversely associated (OR 0.947, 95% CI 0.907–0.989). ANTI tertile comparisons did not reach conventional statistical significance. Sex-specific and restricted-sample analyses were exploratory. Conclusions: A modest inverse association was observed for the continuous ANTI score, but evidence was sensitive to exposure parameterisation. These cross-sectional findings do not demonstrate reduced asthma risk, respiratory benefit, or an inflammatory mechanism. Replication with validated dietary assessment and clinically characterised asthma is needed.

Nutrients doi: 10.3390/nu18213484

Authors: Janay R. Johnson Leslie Hodges Marie E. Thoma

Background: Prenatal participation in the U.S. Department of Agriculture’s Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) improves maternal and infant health. To reduce administrative burden in WIC benefit redemption, the Healthy, Hunger-Free Kids Act required states to adopt electronic benefit transfer (EBT) systems by October 2020; however, the COVID-19 pandemic created a major disruption to this implementation and WIC service delivery. This study examines the impact of state WIC benefit issuance systems on prenatal WIC participation at the time of birth during the COVID-19 pandemic. Methods: We applied a quasi-experimental difference-in-differences approach using U.S. birth certificate data linked to state economic indicators (January 2019–December 2021). The sample included all Medicaid births (n = 4,564,705). States were classified by the type of benefit issuance adopted as of March 2020: online EBT, offline EBT, transitioning to an EBT system, and paper vouchers. Linear probability models were fit with interaction terms between each benefit issuance group and time (pre-pandemic and pandemic 2020 or 2021). Models adjusted for maternal and infant characteristics and state-level economic indicators. Results: Prenatal WIC participation declined during the pandemic in all benefit issuance groups. States transitioning to an EBT system (β = −2.76, 95% CI: −4.61, −0.91 in 2021) or remaining on paper vouchers (β = −3.17, 95% CI: −5.47, −0.87 in 2021) experienced the largest pandemic-related declines compared with online EBT states. We found no significant difference between offline and online EBT groups. Discussion: Adoption of either online or offline EBT systems mitigated WIC participation declines during the pandemic. These findings have implications for ongoing WIC service delivery modernization efforts to safeguard prenatal WIC access from future external shocks.

Nutrients doi: 10.3390/nu18213483

Authors: Ammar Abo Hwach Aysenur Dasdemir Doerte Ahrens Matthias Roeper Ivan Tanev Michael Hansen Mariam Janashia Thomas Rauwolf Mihaela Roxana Popescu Manan Pareek Alexander Schmeisser Ruediger C. Braun-Dullaeus Tarek Bekfani

Background: The phase angle (PhA) derived from bioelectrical impedance analysis (BIA) is a non-invasive marker of cellular integrity that has been associated with nutritional status, functional status and prognosis in heart failure (HF). Whether PhA is related to the skeletal muscle molecular phenotype in HF with preserved ejection fraction (HFpEF) remains unknown. Methods: In this exploratory subanalysis of the SAUNA-HFpEF trial, 17 patients with HFpEF underwent BIA with assessment of body composition, cardiopulmonary exercise testing, isokinetic assessment of quadriceps muscle strength, and measurement of circulating growth differentiation factor-15 (GDF-15), as well as nutrition-related and metabolic laboratory parameters before and after a 10-week sauna intervention. Paired vastus lateralis biopsies (n = 12) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) for catabolic (FBXO32, GSK-3β), fatty acid metabolism (ACADL, CPT1B, CD36), and anabolic (mTOR, IGF-1) markers. Associations with PhA were assessed using Spearman correlation and repeated-measures correlation (rmcorr), with false discovery rate (FDR) correction for multiple testing. Results: Cross-sectionally, lower baseline PhA correlated with higher GDF-15 (r = −0.758; 95% CI −0.936 to −0.412), higher extracellular water to total body water (ECW/TBW) ratio (r = −0.744; 95% CI −0.941 to −0.350), higher expression of GSK-3β, ACADL, FBXO32, CD36, and CPT1B (all r ≤ −0.620), and lower isokinetic quadriceps strength (r = 0.523) (all FDR-adjusted p < 0.05). No significant associations were found for IGF-1, mTOR, or muscle mass. An exploratory comparison using a previously published PhA cut-off of 4.65° showed consistent differences. Longitudinally, PhA did not change significantly over the intervention, and longitudinal changes in PhA were unrelated to changes in molecular markers but correlated with changes in the ECW/TBW ratio (rmcorr r = −0.708; 95% CI −0.883 to −0.360). Body composition, waist circumference, the lipid profile, HbA1c and iron status were also assessed at both time points without any observed changes (all FDR-adjusted p > 0.05). Conclusions: In this small exploratory analysis, lower PhA was associated with a more catabolic and metabolically altered skeletal muscle gene expression profile in HFpEF. PhA may provide complementary, non-invasive information on muscle quality and cellular and fluid status. Its potential role in identifying patients who warrant a structured nutritional assessment deserves further investigation. These hypothesis-generating findings require validation in larger prospective studies.

Nutrients doi: 10.3390/nu18213482

Authors: Aleksandra Kozłowska

Gestational disorders, including pre-eclampsia, gestational diabetes mellitus, and fetal growth restriction, represent major maternal–fetal health challenges, with limited pharmacological options that can be used safely throughout pregnancy. Flavonoids, a diverse group of plant-derived polyphenols, exert antioxidant, anti-inflammatory, and vasoprotective effects in preclinical models. Translational evidence from these mechanistic studies has increased interest in their potential role in maternal–fetal health. This narrative review evaluates the clinical evidence regarding maternal flavonoid exposure across preconception care, pregnancy complications, postpartum recovery, and offspring health. A comprehensive literature search identified thirteen studies published within the past five years, comprising randomized controlled trials, meta-analyses, and evidence from major prospective birth cohorts. Available clinical evidence suggests that higher dietary intake of flavonoid-rich fruits, berries, and vegetables is associated with a lower risk of gestational diabetes, gestational hypertension, and small-for-gestational-age births. Clinical studies of targeted supplementation with specific compounds, including quercetin, epigallocatechin gallate, and botanical extracts, have reported potential benefits in selected clinical settings, including endocrine and reproductive outcomes in women with polycystic ovary syndrome, blood pressure management in pre-eclampsia, and postpartum or post-cesarean pain. Furthermore, maternal flavonoid exposure has been associated with differences in offspring immune development and a potentially lower incidence of food allergies in early childhood. Overall, current clinical evidence supports further investigation of dietary flavonoid intake and selected flavonoid-based interventions in maternal–fetal medicine. Overall, while current evidence strongly supports habitual consumption of a varied, plant-rich diet naturally high in flavonoids during pregnancy, clinical data remain insufficient to recommend routine high-dose isolated flavonoid supplementation in standard obstetric practice.

Nutrients doi: 10.3390/nu18213480

Authors: Dana Mihaela Ciobanu Anca-Elena Crăciun Adriana Rusu Ruben Emanuel Nechifor Nicu Cătălin Drăghici Andreia Mocan Cornelia Bala

Background/Objectives: Eating for pleasure rather than hunger is widespread in the modern food environment. The Reward-Based Eating Drive Scale (RED-13) captures three dimensions of reward-related eating: lack of satiety, loss of control over eating, and preoccupation with food. This cross-sectional study aimed to evaluate the relationship between resting-state functional magnetic resonance imaging (fMRI) metrics and the RED-13 subscales. Methods: RED-13 scores, subjective food appetite, and resting-state brain function were measured in 99 participants between March 2022 and May 2023. Brain function was assessed using degree centrality (DC), regional homogeneity (ReHo), and voxel-mirrored homotopic connectivity (VMHC). Results: Loss of control over eating and preoccupation with food positively correlated with appetite for high fat, high sweet, and low sweet foods. Loss of control over eating positively correlated with DC in the left cerebellar lobule IX (r = 0.416), ReHo in the left brainstem (r = 0.399), and VMHC in the right and left brainstem (r = 0.432) and negatively with ReHo in the right calcarine sulcus (r = −0.434). The lack of satiety subscale positively correlated with ReHo in the left superior frontal gyrus (r = 0.389). The preoccupation with food subscale positively correlated with DC and ReHo in the right middle frontal gyrus. Conclusions: Reward-based eating measured by RED-13 is associated with distinct patterns in the resting-state fMRI metrics within reward processing and cognitive control. These neural correlates, supported by the association of RED-13 with appetite, are consistent with the hypothesis that RED-13 captures a trait-like disposition toward reward-driven eating that might be reflected in the resting-state brain activity.

Nutrients doi: 10.3390/nu18213481

Authors: Aya Fujii Yukihiro Yoshimura

Background: Pubertal sucrose intake is a public health concern, but its effects on cholesterol metabolism and male reproductive endocrinology remain poorly understood. Rodent studies of this window have generally used 30% (w/v) sucrose or 20% (w/v) fructose solutions; beverage-like concentrations have been examined less often. Reported effects of dietary sugar on circulating testosterone are inconsistent; we hypothesized that differences in developmental stage might account for this discrepancy. Methods: Male ICR (Institute of Cancer Research) mice had free access to a 10% (w/v) sucrose solution from 4 to 8 weeks of age. We assessed hepatic and plasma lipids, testicular cholesterol and testosterone, hepatic acetyl-CoA carboxylase (ACC) and AMPK phosphorylation, and expression of cholesterol metabolism- and steroidogenesis-related genes. All measurements were performed after a 16 h fast, during which the sucrose solution was replaced with water. Results: Sucrose selectively elevated hepatic and plasma cholesterol without altering triglycerides, the circulating increase being confined to the non-high-density lipoprotein fraction. Phosphorylation of ACC1 and ACC2 rose while AMPK phosphorylation was unchanged. Peritesticular fat weight increased despite unchanged body weight and energy intake. In the testes, cholesterol content and several steroidogenic transcripts increased, whereas steroidogenic enzyme protein was unchanged. Plasma testosterone increased, whereas intratesticular testosterone did not. Conclusions: In male ICR mice, a 10% (w/v) sucrose solution during puberty supplied approximately 25% of total energy intake, with a comparable fall in solid-chow intake; it was associated with a cholesterol-predominant rather than triglyceride-predominant lipid response and higher circulating testosterone. Testicular cholesterol content and plasma testosterone were both higher while steroidogenic enzyme protein was unchanged, indicating an association between the two rather than a change in steroidogenic capacity.

Nutrients doi: 10.3390/nu18213479

Authors: Sunhye Shin Chan Yoon Park

Depression is one of the most prevalent and disabling psychiatric disorders worldwide and has a heterogeneous pathophysiology involving interacting neurobiological, neuroimmune, and metabolic processes. Alterations in neurotransmission, neuroinflammation, oxidative stress, gut–brain communication, hypothalamic–pituitary–adrenal axis dysregulation, and immunometabolic homeostasis may provide biological links between nutrition and depression. This narrative review examines current evidence linking nutrition and depression across mechanistic, observational, and clinical levels. Regarding dietary patterns, observational evidence generally associates greater adherence to the Mediterranean diet with more favorable depression-related outcomes, while evidence for the DASH diet remains more limited. In contrast, Western dietary patterns and greater consumption of ultra-processed foods are associated with higher risks of depression-related outcomes. Individual nutrients, including omega-3 polyunsaturated fatty acids, vitamin D, vitamin C, folate, vitamin B12, vitamin B6, and essential minerals, have also been investigated in relation to depression, but findings from supplementation studies vary across nutrients, study populations, and baseline nutritional status. However, much of the evidence linking nutritional factors with depression is observational and does not establish causality. Clinical trials of nutrient supplementation and dietary interventions have reported potential benefits in some populations, but findings remain heterogeneous, and large prevention trials have also reported null results. Differences in baseline nutritional status, depression phenotype, and metabolic and inflammatory profiles may partly contribute to this heterogeneity. Future well-designed clinical trials, together with advances in multi-omics and precision approaches, may help identify individuals most likely to benefit from targeted nutritional strategies.

Nutrients doi: 10.3390/nu18213478

Authors: Radmila Matijevic Milan Milinkov Stefan Janicic Srdjan Sarac Nikola Slokar Dora Selesi

Objectives: To describe nutritional status in a volunteer cohort of older adults attending community sarcopenia screening and to explore factors associated with risk of malnutrition, with secondary interest in whether nutritional risk coincides with, rather than excludes, higher adiposity. Design: Cross-sectional, single-centre, exploratory analysis. Setting: A community sarcopenia-screening programme in Vojvodina, Serbia, open to volunteers recruited through pensioners’ associations. Participants: Self-selected, community-dwelling volunteers aged 60 years and older. The analytic sample comprised 388 participants with a complete Mini Nutritional Assessment (MNA). Measurements: Nutritional status was assessed with the full MNA. Depressive symptoms (GDS-15), cognition (MoCA), education, handgrip strength, gait speed, and body composition, including visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry, were recorded. The primary analysis was a multivariable logistic regression for risk of malnutrition (at-risk versus normal) using predictors assessed separately from the MNA; the continuous MNA score and body composition were secondary or exploratory. Results: No participant met the criterion for established malnutrition; 52 of 388 (13.4%, 95% CI 10.2 to 17.2) were at risk of malnutrition. Depressive symptoms were the dominant and most robust correlate, in both the binary model (odds ratio 1.29 per GDS-15 point, 95% CI 1.18 to 1.41) and the continuous-score model. Because the MNA includes a depression/dementia item, this association may partly reflect construct overlap and should not be interpreted as wholly external to the nutritional assessment. Lower education was suggestive in the binary model (odds ratio 2.08, 95% CI 0.95 to 4.56) and significant only for the continuous score. Nutritional risk was not concentrated in the leanest participants: after adjustment for age and sex, higher visceral adipose tissue was associated with at-risk status (odds ratio 1.46 per kg, 95% CI 1.02 to 2.10), but this attenuated after adjustment for depressive symptoms and showed no formal effect modification by sex. Comorbidity and marital status were not associated with nutritional risk. Conclusions: In this volunteer, relatively preserved cohort, risk of malnutrition was most strongly associated with depressive symptoms, although the MNA itself includes a depression/dementia item, with a weaker educational gradient, and was not a condition of low body mass; the relationship with visceral adiposity was exploratory and non-independent. These cross-sectional associations support nutritional screening coupled with evaluation of mood, and caution against excluding older adults with normal or high body mass.

Nutrients doi: 10.3390/nu18213477

Authors: Javier Choquet de Isla Javier Riscart-López Ismael Sánchez-Gomar Manuel Bández-Ruiz Ignacio Rosety-Rodríguez Francisco Brenes-Martín Nicolas G. Bazán Elkin Navarro Quiroz Miguel Ángel Rosety-Rodríguez Noelia Geribaldi-Doldán

Background/Objectives: Although creatine supplementation has a theoretical rationale for neuroprotection, public interest has outpaced available scientific evidence. Alzheimer’s disease (AD), a major and growing global health concern, is among the neurodegenerative diseases proposed to benefit from creatine supplementation. This scoping review systematically maps the existing literature on creatine supplementation for AD to identify gaps that limit translational progress. Methods: Following JBI methodology and PRISMA-ScR guidelines, a search in five electronic databases was conducted for preclinical and clinical studies evaluating creatine interventions in AD. The methodological quality of the studies was appraised using the SYRCLE and NIH tools, respectively. Results: Nine unique studies were included. The preclinical models investigated neuron apoptosis, oxidative stress, neuroinflammation, mitochondrial function, cognitive outcomes, and pathophysiological clearance. Conversely, clinical studies were limited to a pilot trial that suggested preliminary tolerability but could not establish causality. This review identifies six limitations within the current evidence: (1) a reliance on acute or non-transgenic animal models that lack construct validity; (2) a need to address sexual dimorphism; (3) a lack of studies exploring administration routes to bypass the blood–brain barrier; (4) a complete lack of independent randomized controlled trials (RCTs), with all clinical evidence originating from a single research group; (5) an absence of research assessing creatine as a preventive strategy; and (6) a shortage of assessment regarding physical syndromes, such as frailty. Conclusions: The scientific evidence for creatine in AD remains preliminary. Future research should prioritize progressive transgenic models, evaluate noninvasive administration routes, investigate effects on frailty, assess long-term preventive efficacy, account for sex as a variable, and transition to rigorous RCTs.

Nutrients doi: 10.3390/nu18213476

Authors: Amy Saxe-Custack Diana Haggerty Jenny LaChance Sarah Egan David Todem

Background/Objectives: This study examined whether engagement in a pediatric fruit and vegetable prescription program (FVPP) offering one $15 prescription during office visits influenced health, hypothesizing that youth improve blood pressure (BP) and weight status after one year. Methods: This non-controlled longitudinal intervention trial included data from caregiver–child dyads at one pediatric clinic (child age 8–16 years). Correlated data models evaluated average longitudinal trends of study endpoints. Causal inference analyses for longitudinal data estimated time-varying effects of the FVPP on outcomes. Results: In total, 304 dyads enrolled. Youth reduced mean body mass index (BMI) percentile (p = 0.02), systolic BP (p < 0.001), and diastolic BP (p = 0.01). Youth also reduced the odds of elevated systolic BP (p < 0.001), diastolic BP (p = 0.004), and overall BP (p = 0.003). Children who redeemed ≥1 prescription reduced BMI percentile compared to counterparts who did not redeem (p = 0.02). Children who redeemed ≥1 prescription between baseline and 6 months reduced odds of obesity or elevated systolic BP at 12 months, with a relative odds ratio of 0.47 (p = 0.01) or 0.51 (p = 0.05), compared to peers who did not redeem. Conclusions: The results suggest that pediatric FVPP engagement may contribute to improvements in key health outcomes, underscoring the need for further investigation.

Nutrients doi: 10.3390/nu18213475

Authors: Maha Almohamad Crystal Cartwright Fred P. Brooks Craig Gundersen Daphne C. Hernandez

Objective: Medical debt is a long-term hardship, typically unplanned, and difficult to resolve. Hunger-coping economic tradeoffs (e.g., choosing between food or another basic need) are smaller financial constraints related to implementing short-term strategies to resolve cash shortages. This study examined associations between long-term financial constraint (medical debt) and engagement in short-term financial strategies (hunger-coping economic tradeoffs) among charitable food assistance (CFA) recipients. Methods: Survey data were collected in 10 Houston-area and 10 Atlanta-area food pantries in 2022. Hunger-coping economic tradeoff experiences were based on affirmative responses to whether anyone in the household ever had to choose between food and five basic needs. Covariate-adjusted logistic regression models were used to assess the relationship between medical debt (defined as unpaid medical bills) and each hunger-coping tradeoff. Results: Among 999 participants (mean age, 55 years), 41% reported medical debt. Participants with medical debt had greater odds of having to choose between paying for food or (1) childcare (AOR = 1.92, 95% CI 1.37–2.69, p < 0.001), (2) utilities (AOR = 2.05, 95% CI 1.59–2.64, p < 0.001), (3) rent/mortgage (AOR = 2.34, 95% CI 1.75–3.14, p < 0.001), (4) transportation/gas (AOR = 2.81, 95% CI 2.05–3.85, p < 0.001), and (5) education (AOR = 2.18, 95% CI 1.42–3.34, p < 0.001). Conclusions: Long-term hardship (i.e., medical debt) was associated with CFA recipients reporting engaging in short-term financial strategies (i.e., hunger-coping economic tradeoffs) to make ends meet. These findings highlight the need to screen CFA recipients for medical debt, economic hardship, and financial management skills, with food pantries serving as key referral points.

Nutrients doi: 10.3390/nu18213474

Authors: Román Illescas-Quiroga Alireza Naderi Juan José Ramos-Álvarez Alberto Pérez-López Raúl Domínguez

Background: Weight manipulation is standard practice in combat sports to compete in lighter divisions, but the thresholds of duration and magnitude impairing performance remain unclear. Objectives: To evaluate the effects of progressive (PWL) versus rapid weight loss (RWL) across three magnitudes of body mass (BM) reduction, moderate (<5%), aggressive (≥5% to <10%), and extreme (≥10% BM), on performance in combat sport athletes. Methods: PubMed, Medline, Scopus, Scielo, and SportDiscus were searched for interventions published from January 2000 to 30 September, 2025. Two independent researchers performed screening, data extraction, and quality assessment (PEDro scale). Results: Twenty reports corresponding to 18 independent studies met the inclusion criteria (mean PEDro score 5.30; fair quality), comprising 363 unique athletes (322 men, 41 women). Extreme weight loss (≥10% BM) via PWL was associated with impaired technical skill, decision-making, and mood profile, although this evidence was derived from only three independent samples. Aggressive RWL (≥5% to <10% BM) through acute dehydration reduced maximal strength, power, and sport-specific fitness in several but not all studies, with deficits still present 24 h after the weigh-in. Moderate reductions yielded heterogeneous findings, with impairments of mood, balance, and resting maximal voluntary contraction in some reports and no significant effects in others. Conclusions: Effects appeared graded by the magnitude of BM reduction, but the evidence is unevenly distributed, and no study examined extreme RWL. Findings should be interpreted with caution.

Nutrients doi: 10.3390/nu18213473

Authors: Renée P. M. Cardinaals Benjamin M. Taylor Miriam E. Clegg Andrew J. Fletcher Stephan Peters Thom Huppertz

Background: Food substitutions can be used for improving dietary performance in different domains, e.g., human health, environmental impact, affordability or cultural preferences. However, the criteria to justify food substitutions are often inconsistent and based on single nutrients such as maintaining volume, protein, energy or culinary equivalence. Such approaches neglect the broader and more complex nutrient profiles that define a food’s overall nutritional value. Methods: This study introduced the application of cosine similarity to enable comparisons of nutrient profiles of foods based on a multitude of nutrients as an important step in food substitutions. Each nutrient was normalized to a fraction of the Reference Daily Intake and represented an axis in a multidimensional space. Subsequently, each food in the dataset (n = 927) was turned into a vector in this space, and the cosine similarity between each pair of vectors was calculated. The effect of nutrient selection was assessed by using six nutrient subsets, differing from 6 to 21 essential nutrients. Results: Cosine similarity provided a quantitative measure of nutrient-profile similarity and revealed similarities across food pairs. For most food categories, we found a broad distribution of cosine similarity values, spanning from 0 to 1. The choice of nutrient subset shifted the results, highlighting the relevance of including a wide range of essential nutrients. Conclusions: We conclude that cosine similarity is a valuable tool in identifying similar nutrient profiles, offering a comprehensive and flexible framework, complementary to nutrient density approaches, for guiding dietary choices across multiple objectives without compromising nutritional quality.

Nutrients doi: 10.3390/nu18213472

Authors: Joerika Ciqueira Denise Sales Patrícia Freitas Cecília Craveiro Aline Lopes Mariana Lopes

Background/Objectives: The uneven distribution of food stores is a key determinant of health inequities. This ecological study aimed to map socioeconomic inequalities in the food environment of Joao Pessoa, Brazil. Methods: Stores were classified into three categories, according to the main type of food sold: unprocessed, processed, or ultra-processed. The Socioeconomic Index of Geographic Context for Health Studies (GeoSES) and its dimensions (Education, Income, Poverty, Material Deprivation, and Mobility) were used to analyze the territory. The association between the number of food stores and socioeconomic indicators was analyzed through thematic maps, correlation coefficients, and negative binomial regression models. Results: A total of 5087 food stores were mapped. A strong positive correlation was observed between the number of stores selling unprocessed foods and the GeoSES index (r = 0.85; p < 0.001), Education (r = 0.83; p < 0.001), Income (r = 0.85; p < 0.001), and Material Deprivation (r = 0.85; p < 0.001), while Mobility showed a moderate positive correlation (r = 0.59; p = 0.04). In the negative binomial regression model, each one-unit increase in the GeoSES index was associated with a 2.05-fold increase in the expected number of stores selling unprocessed foods (RR = 2.05; 95% CI: 1.48–2.84; p < 0.001). Conclusions: The food environment in Joao Pessoa, Brazil was associated with socioeconomic characteristics, with greater availability of unprocessed food stores in higher socioeconomic areas, while ultra-processed food stores were more evenly distributed across the municipality.

Nutrients doi: 10.3390/nu18213471

Authors: Ioana Badiu Tișa Anamaria Cozma-Petruț Elisabeta Ioana Hirișcău Sorana D. Bolboacă

Background/Objectives: Vitamin D is essential for calcium and phosphorus homeostasis and bone mineralization in infancy; serum 25-hydroxyvitamin D [25(OH)D] is its main biomarker. In Romania, data on vitamin D status among infants younger than six months remain limited, despite evidence of suboptimal status in other Romanian pediatric and perinatal populations. This study aimed to assess vitamin D status in infants aged 1–5 months in northwestern Romania and its associations with supplementation dose, feeding type, and season of blood sampling. Methods: This single-center observational study included infants aged 1–5 months. Serum 25(OH)D was interpreted as deficient (<12 ng/mL), insufficient (12–<20 ng/mL), sufficient (20–100 ng/mL), or potentially excessive (>100 ng/mL). Statistical analyses used parametric or non-parametric methods as appropriate to data distribution. Results: The cohort included 124 girls (56.6%) and 95 boys (43.4%; median age 4 [3–5] months). Median serum 25(OH)D was 61.24 [49.53–75.32] ng/mL; 94.5% of infants had sufficient concentrations, deficiency and insufficiency each occurred in 0.9%, and 3.7% had potentially excessive concentrations. Serum 25(OH)D increased progressively with reported supplementation dose (p < 0.0001) and differed by feeding type (p = 0.0279), with breastfed infants having higher concentrations than formula-fed infants. No significant seasonal difference was observed (p = 0.4218). Conclusions: In this hospital-based cohort, most infants had sufficient 25(OH)D concentrations, in a context of near-universal supplementation. Higher reported doses were associated with higher 25(OH)D concentrations, and concentrations >100 ng/mL occurred almost exclusively in infants receiving 2000 IU/day. Without data on calcium metabolism, these concentrations do not indicate vitamin D toxicity, but they support adherence to recommended prophylactic doses.

Nutrients doi: 10.3390/nu18213469

Authors: Marina Barišić Sunčana Včelik Biljana Crevar Tomislav Soldo Maja Miškulin Tihomir Kovač

Hericium erinaceus (Lion’s Mane) is an edible and medicinal mushroom that has attracted increasing scientific interest as a dietary supplement because of its potential effects on cognitive function, neuroprotection, mental well-being and healthy ageing. Its biological activities have been primarily attributed to bioactive compounds such as polysaccharides, hericenones and erinacines, which may influence neurotrophic signalling, neuroplasticity, oxidative stress, inflammation and neuronal survival. This review examines the potential benefits and limitations of H. erinaceus supplementation, with emphasis on its bioactive compounds, mechanisms of action, cognitive and neuroprotective effects, mental-health-related outcomes, safety and product quality. Experimental studies provide evidence for neurotrophic, antioxidant, anti-inflammatory and neuroprotective activities, while clinical studies suggest possible benefits for cognitive outcomes, particularly information-processing speed, subjective stress and well-being. However, findings are inconsistent across study populations and outcomes, and evidence regarding neurodegenerative diseases is still largely derived from preclinical studies. Interpretation is further complicated by small sample sizes, short intervention periods, variability in supplement formulations, differences between fruiting-body-derived and mycelium-derived preparations and insufficient standardisation of bioactive compounds. Although H. erinaceus supplementation is generally well tolerated, its safety during prolonged use and optimal dosage remains unclear. Overall, H. erinaceus shows potential as a dietary supplement for supporting cognitive and neurological health, but further well-designed clinical trials involving larger populations, longer intervention periods and standardised, well-characterised preparations are needed to confirm its clinical effectiveness and establish reliable recommendations for safe supplementation.

Nutrients doi: 10.3390/nu18213470

Authors: Giovanni Albani Paolo Capodaglio Marica Giardini Giuseppe Modaffari Vasuki Ranjani Chellamuthu Yin-Xia Chao Anusha Jayaraman Salvatore Albani Eng-King Tan

Background: Constipation can precede the motor diagnosis of Parkinson’s disease (PD), but its mechanisms are multifactorial. Gut bacteria can metabolize administered levodopa (LD), and enteric dopamine receptors participate in the regulation of motility. These observations motivate, but do not establish, a connection between microbial LD metabolism and constipation. Evidence: Bacterial tyrosine decarboxylase (TDC) converts LD to dopamine in biochemical and animal systems. Human studies associate fecal TDC abundance with some treatment and pharmacokinetic variables, but gene abundance does not measure enzyme activity. A longitudinal PD cohort found an inverse association between constipation severity and TDC abundance in one model, highlighting the need to consider medication effects and reverse causation. Microbiome alterations in risk-enriched populations do not demonstrate increased TDC activity before PD diagnosis. Hypothesis: In a subset of untreated individuals at increased risk of PD, sufficient luminal endogenous L-DOPA might permit microbial dopamine production that influences intestinal transit, provided that the resulting dopamine reaches relevant receptors at effective concentrations. Endogenous substrate availability, anatomical access, and the net balance of dopamine production and clearance are unresolved. After LD treatment begins, a larger exogenous substrate supply creates a distinct setting for drug–microbe interactions. Conclusions: The proposed continuum is conditional and requires biochemical and functional validation before human biomarker development. We propose substrate tracing, comparisons of TDC-positive and TDC-deficient bacteria, receptor-specific testing, and longitudinal gastrointestinal phenotyping. Current evidence does not justify TDC-directed dietary prevention of PD or clinical prediction from fecal TDC abundance alone.

Nutrients doi: 10.3390/nu18213467

Authors: Seong-Uk Baek Jin-Ha Yoon

Background: Dietary quality is important for preventing and managing chronic diseases in older adults; however, its association with respiratory health remains insufficiently understood. This cross-sectional study examined the association between dietary quality and lung function among older adults in South Korea. Methods: This cross-sectional study included 1021 adults aged ≥65 years from the 2024 Korea National Health and Nutrition Examination Survey. Dietary quality was measured using the Korean Healthy Eating Index (KHEI; range, 0–100). The forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, forced mid-expiratory flow between 25% and 75% of FVC (FEF25–75%), and peak expiratory flow (PEF) were measured using spirometry. Linear regression models were used with beta coefficients and 95% confidence intervals (CIs). Results: The mean (standard deviation [SD]) KHEI score was 67.41 (10.97). The mean (SD) values for the lung function parameters were 2.95 (0.72) L for FVC, 2.21 (0.54) L for FEV1, 75.22 (7.68)% for the FEV1/FVC ratio, 1.93 (0.79) L/s for FEF25–75%, and 6.03 (1.73) L/s for PEF. The β (95% CI) for the relationship between the KHEI (unit = 1-SD increment) and lung function outcomes was 0.013 (−0.016–0.041) L for FVC, 0.028 (0.003–0.053) L for FEV1, 0.539 (0.129–0.950) % for the FEV1/FVC ratio, 0.057 (0.010–0.104) L/s for FEF25–75%, and 0.066 (−0.018–0.149) L/s for PEF. Conclusions: KHEI was positively associated with FEV1, FEV1/FVC, and FEF25–75%, whereas no clear associations were observed with FVC or PEF.

Nutrients doi: 10.3390/nu18213468

Authors: Flavia Indrio Luca Pecoraro Pierluigi Manni Valeria Verdesca Antonio Di Mauro

Background: Infant distress syndrome, previously termed Infantile colic, is a common disorder of gut–brain interaction characterized by excessive crying and impaired behavioral regulation. Although Limosilactobacillus reuteri DSM 17938 has shown efficacy in predominantly breastfed infants, treatment responses remain variable, highlighting the need to investigate alternative probiotic formulations. BG-R46™, a strain derived from DSM 17938, exhibits distinct properties in preclinical models, providing a rationale for evaluating the combined formulation. This study investigated the efficacy and tolerability of DSM 17938 plus BG-R46™ compared with placebo in infants with infantile colic. Methods: In this randomized, double-blind, placebo-controlled trial, 50 infants were randomized to receive either the probiotic formulation or placebo for 21 days. Forty-eight infants (24 per group) were included in the intention-to-treat and per-protocol analyses. The primary endpoint was the change from baseline to Day 7 in total infant distress time, defined as the sum of awake fussing, crying, and inconsolable crying recorded using the Baby’s Day Diary®. Secondary outcomes included crying time, infant behavioral regulation (sleep duration, awake and content behavior, awake fussing, and inconsolable crying), maternal emotional well-being assessed using the Edinburgh Postnatal Depression Scale (EPDS), and safety. Results: Baseline infant distress time was comparable between groups. At Day 7, infant distress time decreased by 43% in the probiotic group versus 13% in the placebo group (−236.0 ± 111.5 vs. −66.7 ± 100.1 min/day; p < 0.001). At Day 21, reductions reached 62% and 26%, respectively. The probiotic formulation was well tolerated throughout the study. Conclusions: Supplementation with L. reuteri DSM 17938 plus L. reuteri BG-R46™ significantly reduced infant distress compared with placebo.

Nutrients doi: 10.3390/nu18213466

Authors: Wamidh H. Talib Intisar Hadi Al-Yasari Jomana Alqannas Shahd Mismar Doaa Anbarserry Wafa` A. Ahmad Douglas Law Ahmad Riyad Alsayed Bence Raposa

Cancer is a widespread disease and a leading cause of death worldwide. This has increased interest in foods that contribute to lowering its incidence. Olive oil is a key component of the Mediterranean diet and contains numerous bioactive compounds, including oleuropein, hydroxytyrosol, oleocanthal, squalene, sterols, tyrosol, and oleacein, which possess various properties and benefits. This review examines the potential of these compounds as anticancer agents and their ability to manage various types of cancer. Chemical structure, mechanisms of action, and potential to work in combination with conventional treatments were discussed for each compound. Studies discussed in this review show promising anticancer effects of olive oil compounds with high potential to augment conventional treatments through the anticipated anticancer effect of the Mediterranean diet with olive oil. This review focused on in vitro and preclinical studies of using olive oil phytochemicals in cancer research. However, further clinical and experimental studies are needed to determine the optimal dosage of olive oil and better confirm its therapeutic efficacy.

Nutrients doi: 10.3390/nu18213465

Authors: Won-Min Lee Kie Hwan Chun Won Byong Yoon Byung-Hoo Lee Hyun-Seok Kim

Resistant starch (RS), which is resistant to upper gastrointestinal digestion with minimal postprandial glycemic impact, serves as an effective nutritional strategy for mitigating diet-induced obesity and associated metabolic dysfunctions. In this study, starch citrate with a degree of substitution (0.087) and high RS content (83.7%) was synthesized via sequential reactive extrusion and dry-heat treatment, and its anti-obesity efficacy was evaluated in C57BL/6NCrljOri mice fed a gelatinized high-starch diet (HSD). Mice fed the gelatinized HSD exhibited significant increases in body weight and visceral adiposity alongside impaired glucose tolerance, demonstrating an obesogenic phenotype under the present dietary conditions. Dietary supplementation with starch citrate dose-dependently attenuated excess fat accumulation, suppressed epididymal adipocyte hypertrophy, and preserved systemic glucose homeostasis. Furthermore, starch citrate modulated circulating adipokine levels and improved selected serum lipid profiles, while complete starch citrate substitution significantly downregulated hepatic protein expression associated with de novo lipogenesis and adipogenic transcriptional regulation. Consequently, starch citrate demonstrates significant preventive potential against diet-induced obesity and associated metabolic complications, including dyslipidemia and impaired glucose homeostasis. Overall, these findings suggest that starch citrate may serve as an RS-rich eco-friendly functional food ingredient with the potential to attenuate metabolic dysfunctions and obesity triggered by the consumption of rapidly digestible carbohydrates.

Nutrients doi: 10.3390/nu18213464

Authors: Marco Cintoni Elena Leonardi Elisabetta Meo Pauline Celine Raoul Marta Palombaro Emanuele Rinninella Lucia Parroni Esmeralda Capristo Antonio Gasbarrini Maria Cristina Mele

Cancer-associated cachexia and chronic systemic inflammation remain among the most challenging complications in oncology, impairing prognosis, treatment tolerability, and survival. This narrative review examines the mechanistic rationale and clinical evidence for omega-3 polyunsaturated fatty acids (PUFAs), principally eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as adjunctive nutritional and metabolic support agents in this setting, drawing on randomized controlled trials, systematic reviews, meta-analyses, and mechanistic studies, alongside the oral, enteral, parenteral, and nanotechnology-based platforms used to deliver these fatty acids. In experimental models, predominantly cancer cell lines and tumor-bearing rodents, EPA and DHA act on multiple oncological processes, including suppression of pro-inflammatory cytokine synthesis, remodeling of the tumor microenvironment, inhibition of tumor cell proliferation, induction of apoptosis, and attenuation of skeletal muscle catabolism via the ubiquitin-proteasome system and the IGF-1/PI3K/Akt/mTOR axis; in patients, the most consistent mechanistic correlate is a reduction in circulating inflammatory biomarkers. Bioavailability varies substantially by molecular form, with re-esterified triglycerides outperforming ethyl esters and emerging micellar and phospholipid nanoformulations achieving markedly higher absorption in pharmacokinetic and preclinical studies. In advanced non-small cell lung cancer with established cachexia, a meta-analysis of small randomized trials suggests that at least 2 g EPA+DHA per day for six weeks or more may yield modest gains in body weight and quality-of-life scores; this signal, however, derives mainly from pooled analyses and has not been consistently reproduced in individual trials, including large negative trials in mixed cancer populations. Across broader oncological populations, reduction in inflammatory biomarkers is the most consistent finding, effects on chemotherapy tolerability are suggestive but of low certainty, and effects on lean mass and overall survival remain inconclusive. Consistent with ESPEN and ESMO guidance, omega-3 PUFAs should be regarded as metabolic and nutritional support within multimodal cachexia care, not as an anticancer treatment. Omega-3 PUFAs are a biologically grounded and potentially useful, but not yet clinically established, intervention in oncological nutrition, but adequately powered trials with harmonized endpoints, standardized formulations, and stratification by cancer type and cachexia stage are still needed to translate this mechanistic signal into definitive therapeutic protocols.

Nutrients doi: 10.3390/nu18213462

Authors: Solveig I. N. Watters Mari C. W. Myhrstad Elisabeth Austad Line Gaundal Henrik M. Roager Terje F. Gjøvaag Monica J. Hellmann Lisa Garnweidner-Holme Lise Friis Pedersen Knut E. A. Lundin Christine Henriksen Vibeke H. Telle-Hansen

Background: The only treatment for coeliac disease (CeD) is a gluten-free diet. Gluten-containing cereals constitute a major source of dietary fibre, raising concerns about fibre intake for individuals with CeD. Objective: The present study aimed to investigate the effect of pseudocereal-based, fibre-rich gluten-free products on glycaemic regulation in women with CeD. Secondary endpoints were changes in gut symptoms, targeted gut microbial taxa, and inflammatory and metabolic markers. Methods: This double-blind, randomised, controlled trial was conducted remotely and included 30 women with CeD. Participants were allocated to consume either pseudocereal-based, fibre-rich gluten-free products (experimental) or benchmark products (control) for three weeks. Before and after the interventions, participants underwent an oral glucose tolerance test (OGTT), reported gastrointestinal symptoms, and provided blood samples to analyse micronutrients, metabolic markers, and a satiety hormone, and faecal samples for targeted gut microbial taxa analyses. Results: There was no significant difference in the glycaemic response after the intake of fibre-rich products compared with control products. However, a significant reduction in glucose iAUC was observed within the experimental group (p = 0.049). There was no significant change in gut symptoms within or between groups, except for a reduction in diarrhoea in the control group compared with the experimental group. The abundance of five bacterial species was significantly decreased after intake of control products compared to experimental products. Conclusions: Pseudocereal-based, fibre-rich gluten-free products may be included in the diet for women with CeD without affecting gastrointestinal symptoms. Whether these fibre-rich products improve glycaemic regulation and exert effects via alterations in the gut microbiota needs to be further investigated.

Nutrients doi: 10.3390/nu18213463

Authors: Anna Maria Martone Elena Levati Riccardo Calvani Matteo Tosato Vincenzo Galluzzo Francesca Ciciarello Sara Salini Stefano Cacciatore Emanuele Marzetti Francesco Landi

Background: Unhealthy dietary patterns are a major risk factor for death and functional disability. Food labeling provides key nutritional information and is associated with healthier dietary patterns. This study aims to investigate whether attention to food labels is associated with dietary patterns, BMI, and Cardiovascular 8 metrics scores. Methods: We analyzed data from the Look-Up 8+ project, including adults aged 18 years or older from several Italian regions. Participants underwent a comprehensive lifestyle assessment, including dietary habits, cholesterol and glucose measurements, and anthropometric evaluations. Descriptive, comparative, and inferential statistical analyses were used to investigate the association between attention to food labels and dietary patterns, BMI, and Cardiovascular Health scores. Results: Among 7401 participants (mean age 54.4 ± 15.0 years, with 55.5% women), those who reported reading food labels exhibited a higher prevalence of regular physical activity and adherence to a healthy diet. In contrast, participants who did not read food labels had a higher body mass index. Both men and women who reported greater attention to food composition had a higher Life’s Essential 8 score. Conclusions: These results suggest that attention to food labels is associated with more favorable lifestyle choices and improved cardiovascular health profiles.

Nutrients doi: 10.3390/nu18213461

Authors: Ioana Cristina Crivei Roxana Nicoleta Ratu Ionuț-Dumitru Veleșcu Andreea Bianca Balint Florin Daniel Lipșa Florina Stoica Luciana Alexandra Crivei

Food additives are defining components of ultra-processed foods, yet microbiome-related effects remain largely outside routine safety assessment. This review evaluates evidence for six additive classes across four pathways—microbial community changes, altered microbial metabolites, mucus-epithelial barrier disruption, and immune modulation—and examines how these findings could inform microbiome-inclusive risk assessment. Mechanistic, translational, and epidemiological evidence was organized using a five-tier hierarchy: in vitro, ex vivo, animal, observational, and controlled human studies. Chronic-disease associations were graded across six domains by two raters using explicit criteria, with sensitivity analysis. Evidence was then translated into a tiered, decision-gated assessment protocol, illustrated with carboxymethylcellulose and back-tested against carrageenan, acesulfame K, and titanium dioxide, which return three different protocol outcomes. Non-nutritive sweeteners and emulsifiers have the strongest direct human and ex vivo evidence, including microbiome-dependent interindividual responses, although null and discordant trials remain. Gastrointestinal and metabolic outcomes received the highest support, cardiovascular associations were intermediate, and autoimmune, neurological, and psychiatric links remained preliminary. Metabolic and cardiovascular epidemiology relied largely on NutriNet-Santé, with modest hazard ratios (generally 1.03–1.15 per exposure increment) and indirect exposure estimation. Recent additive-mixture analyses from the same cohort were also considered. Food additives can act as context-dependent, microbiome-active exposures. Current evidence supports considering microbiome composition, barrier-integrity, and immune endpoints in additive safety evaluation, while causal links with most chronic-disease outcomes remain unproven.

Nutrients doi: 10.3390/nu18213460

Authors: Judith Raya-Muñoz Blanca Maria del Castillo Martinez Marta Freixas Bermejo Marina Álvarez-Beltrán Vanessa Cabello-Ruiz Susana Redecillas-Ferreiro Oscar Segarra-Cantón

Background/Objectives: Copper deficiency is described in adults on prolonged jejunal enteral nutrition, but paediatric evidence remains scarce. We compared the prevalence, timing and consequences of copper and other micronutrient deficiencies in children on prolonged jejunal versus gastric enteral nutrition. Methods: Ambispective observational cohort study at a tertiary paediatric centre. Children aged 0–18 years receiving at least 80% of their nutritional requirements through an enteral device for more than three months were studied; pre-existing malabsorption was an exclusion criterion. Groups were defined by feeding route (jejunal or gastric). Serum copper, zinc, iron and selenium were assessed longitudinally, with concurrent C-reactive protein < 2 mg/dL. Results: Forty-six patients were included (jejunal, 31; gastric, 15). Copper deficiency occurred in 9 of 31 jejunal patients (29.0%) and in no gastric patient (risk difference 29.0%, 95% CI 4.9–46.6%; p = 0.021). Iron deficiency was the commonest abnormality (71% versus 60%; p = 0.51). Six of the nine copper-deficient children developed anaemia or neutropenia; all normalised after oral copper sulfate given through the gastric route. Conclusions: In this single-centre cohort, prolonged jejunal feeding was associated with more frequent copper deficiency despite adequate intake; larger studies should confirm this. We suggest monitoring serum copper from three months after post-pyloric feeding starts.

Nutrients doi: 10.3390/nu18203459

Authors: Vlad Sabou Heather Z. Macrae Kevin Mulholland Daniel Webber Liam R. Brown Rebecca K. Randell Caroline A. Tarnowski Lewis James Ian Rollo

Background/Objectives: Hypohydration increases physiological strain and reduces physical and technical soccer performance. Nonetheless, there are limited data on fluid balance responses in elite soccer players training in cool environments. This study investigated sweat and fluid/carbohydrate intake responses in elite male professional soccer players training at a high intensity in cool environments. Methods: Fluid/sodium (Na+) losses and ad libitum carbohydrate/fluid intake of thirty-six elite male soccer players were measured as part of four training sessions, with each player completing the measurements once. Data were collected under the following conditions classified by ambient temperature (11.3 ± 2.1 °C), wet bulb globe temperature (9.8 ± 3.0 °C), and relative humidity (76.8 ± 10.2%). Mean duration of training sessions was 70 ± 4 min and included soccer-specific training, with players covering a mean total distance of 7054 ± 654 m and 104 ± 9 (m·min−1). Before and after exercise, players were weighed in minimal clothing. During training breaks, players had ad libitum access to carbohydrate beverages and water. Sweat [Na+] (mmol·L−1) was measured by absorbent patches positioned on the upper back. Results: Two out of eleven players displayed a USG score indicative of ‘minimal hypohydration’ (1.022 and 1.022, respectively). Seventeen percent of players experienced hypohydration > 2% of pre-exercise body mass. Mean sweat rate was 1.5 ± 0.4 L·h−1, with individual sweat rates ranging from 0.4–2.2 L·h−1 (outfield players, n = 33). Goalkeepers mean sweat rate was 0.7 ± 0.2 L·h−1 (range 0.6–0.9 L·h−1, n = 3). Sweat [Na+] also varied substantially between players (range 21–49 mmol·L−1), with a mean sweat [Na+] of 35 ± 6.8 mmol·L−1. There was a significant positive correlation between sodium chloride loss and intensity of play (m·min−1) covered during training (rs = 0.368, p = 0.049). Carbohydrate ingestion during training varied between individuals (range 0–25 g·h−1). Conclusions: Sweat rate and sweat sodium chloride loss varies in elite soccer players during high-intensity training in cool environments. Hypohydration exceeded 2% pre-exercise body mass in 17% of players. The ad libitum carbohydrate intake of the players was below recommendations given the intensity and duration of the training sessions.

Nutrients doi: 10.3390/nu18203458

Authors: Jean Paul Vergara-Aguilar Angélica Lizcano Adriana Martinez-Perez Yamile Calle-López Mackenzie C. Cervenka Carlos A. Clavijo-Prado Juan Camilo Cotuá-Urzola Walter González Dahyana K. González-Velásquez Malena C. P. Grillo-Ardila Paula Martinez-Micolta Lina M. Ramírez Nataly Rincón-Franco Juliana Vargas Osorio Lyda V. Villamil-Osorio Adriana Tanner

Background/Objectives: Drug-resistant epilepsy affects up to one-third of patients with epilepsy and is associated with higher morbidity, mortality, trauma events, psychosocial challenges, and decline in quality of life. In Latin America, disease burden is high and access to advanced therapies remains limited. Ketogenic Diet Therapy (KDT) has been shown to be beneficial in adults, but its implementation requires standardized protocols and experienced multidisciplinary teams. This study aimed to develop practical, evidence-based recommendations to guide the indication, implementation, and follow-up of KDT in adults with drug-resistant epilepsy through expert consensus in Colombia. Methods: A modified version of the Nominal Group Technique was used to develop, discuss, and vote on management concepts. Clinical questions were structured using the PICO framework. Literature searches were conducted in PubMed and EMBASE for articles published since 2015, and the evidence was integrated with the experience of a multidisciplinary expert panel. Results: Twelve recommendations were issued, covering commercial formulas, induction and follow-up protocols, individualized dietary interventions, safety, diagnostic support, nutritional supplementation, and drug-diet interactions. The consensus highlights the need for interdisciplinary teams, structured education, early adherence strategies, and close follow-up, and the role of enteral emergency formulas in intensive care settings. Conclusions: Evidence around KDT shows it can be implemented safely as an adjunctive treatment for adults with drug-resistant epilepsy and is reasonable to consider following the failure of two adequate antiseizure medications. Structured implementation may reduce seizure frequency, improve quality of life, and reduce the pharmacological burden. Multicenter prospective studies are needed to further assess efficacy, safety, and resource utilization. These recommendations contribute to closing the gap between evidence and clinical practice.

Nutrients doi: 10.3390/nu18203455

Authors: Dominika Granda Andrzej Pokrywka Maria Karolina Szmidt Olga Surała Karol Jędrejko Sylwia Lewandowska-Pachecka Grażyna Nowicka

Background/Objectives: Premenstrual syndrome (PMS) and dysmenorrhea can impair training performance in female athletes. Botanical ingredients are commonly used to manage these conditions in the general population, but it is unknown whether elite female athletes do so. This study aimed to identify botanical ingredients evaluated in studies for PMS and dysmenorrhea and determine whether elite female athletes declared them on Doping Control Forms (DCFs). Methods: A narrative literature review was conducted to identify botanical ingredients evaluated in studies for PMS and dysmenorrhea. Then, DCFs completed during routine anti-doping testing among elite athletes in Poland (2018–2023) were analyzed for declarations of these ingredients, both directly and as components of multi-ingredient products. The proportion of DCFs containing these ingredients was compared between female (n = 4451 DCFs) and male athletes (n = 9068 DCFs; reference) using chi-squared tests. Results: The review identified 8 and 21 botanical ingredients with evidence for PMS and dysmenorrhea, respectively; of which 9 were detected in DCFs. The most commonly declared ingredients among female athletes were ginger and turmeric/curcuminoid (1.75% and 1.26%, respectively, both studied for PMS and dysmenorrhea). Chasteberry, on the other hand, with the most extensive, albeit low-confidence evidence, for PMS, was rarely declared (0.22%). Direct declaration of ginkgo, valerian, evening primrose oil, and chasteberry was significantly more common among female than male athletes (0.22% vs. 0.02%, 0.36% vs. 0.03%, 0.47% vs. 0.03%, 0.22% vs. 0.02%; adjusted p < 0.05). Conclusions: Declarations of botanical ingredients studied for PMS and dysmenorrhea were infrequent on DCFs completed by female athletes. Because DCFs do not record the reason for use, these data cannot establish whether declarations reflected treatment of menstrual symptoms; studies assessing indication, symptom status and motivation are needed.

Nutrients doi: 10.3390/nu18203457

Authors: Kinga Kot Ola Sobieska-Poszwa Agnieszka Dobrowolska Iwona Krela-Kaźmierczak Ewa Misterska

Background: Self-related cognitive schemas may influence psychological adaptation to chronic illness. However, their role in adults with celiac disease (CD) remains poorly understood. We aimed to assess cognitive schemas and depressive symptoms in adults with CD compared with healthy controls, and to examine their associations with perceived disease burden. Methods: This cross-sectional comparative study included 96 adults with CD and 96 healthy controls. Participants completed the Cognitive Triad Inventory (CTI) and Beck Depression Inventory (BDI), and sociodemographic and clinical data were collected. Perceived disease- and diet-related burden was assessed using investigator-developed single-item measures. Results: The mean age at CD diagnosis was 33.6 (SD 13.4) years, and the mean duration of symptoms before diagnosis was 5.4 (SD 5.1) years. Adults with CD reported higher depressive symptom scores than healthy controls (8.4 (SD 7.9) vs. 6.6 (SD 8.0); Mann–Whitney U = 3850.5, Z = 1.99, Cohen’s d = 0.29, p = 0.046). No significant between-group differences were observed in total CTI scores or its Self-view, World-view, or Future-view subscales. After adjustment for age, sex, educational level, marital status, and employment status, neither BDI nor CTI scores were independently associated with group membership. Exploratory bivariate analyses within the CD group showed that higher Self-view scores were associated with lower perceived negative impact of gluten-free diet requirements on family life (rS = −0.29, p = 0.004) and lower perceived impact of CD symptoms and disease exacerbations on everyday life (rS = −0.31, p = 0.002). These associations remained statistically significant after Bonferroni correction. Conclusions: Adults with CD reported slightly higher depressive symptom levels than healthy controls, whereas cognitive schemas did not differ significantly between groups. The observed associations between CTI Self-view and selected indicators of perceived disease- and diet-related burden warrant further investigation, but do not establish a causal contribution of self-view to disease burden.

Nutrients doi: 10.3390/nu18203456

Authors: Saya Nosaka Fumiya Kawase Tomoko Imai Ayako Sezaki Keiko Miyamoto Chisato Abe Masayo Sanada Norie Sugihara Toshie Honda Yuta Sumikama Ayaka Inden Takayoshi Tsukahara Hiroshi Shimokata

Background/Objectives: National food environments may be associated with cardiovascular risk, but how their association with country-level ischemic heart disease (IHD) mortality differs across diet-quality indices remains unclear. We compared six food supply-based dietary scores calculated using 2010 food data in relation to annual IHD mortality from 2010 to 2021. Methods: We conducted a longitudinal study of 148 countries with populations ≥ 1 million. Using 2010 FAOSTAT Food Balance Sheet data, we calculated the Dietary Approaches to Stop Hypertension (DASH) score, the Alternative Healthy Eating Index (AHEI), Mediterranean Diet Score (MDS), Traditional Japanese Diet Score (TJDS), Planetary Health Diet Index (PHDI), and Quantitative Index for Dietary Diversity (QUANTIDD). The outcome was age-standardized IHD mortality during 2010–2021. Associations between time-invariant baseline dietary scores and annual IHD mortality were assessed using multivariable-adjusted linear mixed-effects models. Effect sizes were expressed as mortality rate ratios (MRRs) per 1-standard deviation (SD) higher score; model fit was compared using Akaike information criterion (AIC) weights and marginal R2, and effect estimates were compared pairwise. Results: Higher DASH and AHEI scores were associated with lower IHD mortality. MRRs per 1-SD higher score were 0.914 (95% confidence interval, 0.849–0.983) for DASH and 0.908 (95% confidence interval, 0.838–0.985) for AHEI. No significant associations were observed for MDS, TJDS, PHDI, or QUANTIDD. DASH had the highest AIC weight (0.434), followed by AHEI (0.341), with a slightly higher marginal R2 for DASH. Pairwise comparisons showed no statistically significant differences in effect estimates between DASH and AHEI or between either of these scores and the other dietary scores. Conclusions: Higher baseline DASH and AHEI scores were associated with lower IHD mortality during 2010–2021, with similar effect estimates per 1-SD higher score and broadly comparable model fit. However, direct pairwise comparisons revealed no statistically significant differences in standardized effect sizes between these scores (DASH and AHEI) and the other dietary scores. These findings suggest that the relevance of dietary scores may depend on the outcome and analytic context rather than the superiority of a single index. Because this was an ecological study, these findings should not be interpreted as individual-level causal effects.

Nutrients doi: 10.3390/nu18203454

Authors: Carla Gonçalves Tânia Silva-Santos Pedro Moreira

Background: Excessive sodium intake is a major modifiable risk factor for hypertension and cardiovascular disease and remains well above recommended levels globally. Although sodium reduction strategies have traditionally focused on individual behaviour change, food environments largely determine sodium consumption by shaping food availability, affordability, preferences, and purchasing options. However, no conceptual framework has specifically characterized food environments according to their capacity to promote excessive salt intake. Objectives: To introduces the concept of the salinogenic food environment and proposes a conceptual framework integrating environmental determinants of sodium exposure across food systems, dietary behaviors and cardiovascular health outcomes. Methods: A narrative conceptual review synthesized evidence from ecological health models, particularly the ANGELO framework, food environment research, sodium epidemiology, dietary behaviours, and cardiovascular health. Evidence from retail, out-of-home and institutional food settings, sociocultural and economic influences, and policy environments informed framework development. Results: The salinogenic food environment is defined as an environment that promotes high salt intake through the widespread availability of high-sodium foods and the reinforcement of salty taste preferences. The framework encompasses four interrelated domains: physical, economic, sociocultural, and policy/governance environments. Evidence indicates that processed and ultra-processed foods, restaurant and institutional meals, food pricing structures, cultural dietary practices, and insufficient regulatory measures collectively contribute to excessive sodium exposure. The framework highlights how these domains interact to shape sodium exposure, reinforce salty taste preferences, and contribute to socioeconomic inequalities in sodium intake. It also proposes approaches for operationalizing salinogenic environments through objective indicators, perceived environment measures, and composite indices. Conclusions: The salinogenic food environment framework reorients sodium reduction from an individual responsibility toward to a structural property of contemporary food systems. By providing a common conceptual language for research, surveillance and policy evaluation, it may facilitate the development of more effective multisectorial strategies to reduce sodium exposure and improve cardiovascular health.

Nutrients doi: 10.3390/nu18203453

Authors: Mireia Escudero-Marín Hatim Azaryah Andrea De La Garza Carmen López-Sabater Rocío Bonillo-León Luz María García-Valdés Elvira Verduci Cristina Campoy

Background: Maternal obesity is associated with altered polyunsaturated fatty acid (PUFA) status during pregnancy and may programme offspring adiposity, yet the contribution of specific n-3 and n-6 PUFAs across gestation and in cord blood to childhood body composition remains incompletely understood. We investigated these associations between maternal PUFA status during pregnancy and offspring obesity-related outcomes at 8.5 years. Methods: Here, we analysed data of 172 mother–child pairs from the PREOBE cohort, grouped by maternal pregestational body mass index (BMI) as normal weight (NW, n = 84), overweight (OW, n = 47), or obese (OB, n = 41). Plasma phospholipid PUFAs were quantified at 24, 34, and 40 weeks of gestation and in cord blood. At 8.5 years, children underwent anthropometry and body-composition assessment by skinfolds and bioelectrical impedance, remaining 104 mother–child pairs with valid data. Associations analyses included ANOVA/ANCOVA adjusted by confounders variables, unadjusted bivariate Spearman rank correlations with Benjamini–Hochberg False Discovery Rate (FDR) correction, and pooled robust linear regression. Results: Compared with NW mothers, OW and OB mothers showed lower α-linolenic acid (ALA) and docosahexaenoic acid (DHA) and higher n-6 PUFAs and n-6/n-3 ratios during pregnancy. Cord γ-linolenic acid (GLA) was inversely associated with several adiposity measures in the NW and OW groups after FDR correction. No correlation in the OB group met the FDR threshold; the inverse cord GLA–fat-free mass index (FFMI) association was nominal only (ρ = −0.52, p = 0.016, q = 0.688). In pooled regression models, cord GLA was inversely associated with BMI-for-age z-score, waist circumference z-score, waist-to-height ratio, body fat mass percentage, and fat mass index (FMI), whereas maternal GLA at 40 weeks was positively associated with body fat mass percentage and FMI. These pooled estimates do not establish group-specific effects. Conclusions: Maternal and cord-blood PUFA profiles were associated with childhood body composition, with patterns that varied descriptively by sampling time and maternal BMI group. These observational findings do not establish causality, protection, or differences between groups in the strength of association. Mechanistic and interventional research is required before individualised long-chain PUFA monitoring or supplementation can be recommended for obesity prevention.

Nutrients doi: 10.3390/nu18203452

Authors: Beulah Favour Ortutu Kyeong-sook Keum Jin Gyeom Kim Su-In Yoon Jin Ah Cho

Background: Sucralose is widely used as a non-nutritive sweetener, yet its systemic consequences of long-term exposure remain incompletely understood. This study investigated the effects of long-term sucralose consumption on metabolic homeostasis and neurobehavioral outcomes. Methods: Male C57BL/6J mice were treated with 5 mg/kg body weight sucralose under non-stressed and unpredictable chronic mild stress conditions for 14 weeks. Results: Sucralose altered hepatic cholesterol regulation without significantly increasing serum triglyceride or total cholesterol relative to water controls. Significant treatment–stress interactions were detected for hepatic Srb1 (F = 6.511, p = 0.004) and intestinal Npc1l1 (F = 3.763, p = 0.032), indicating stress-dependent modulation of cholesterol absorption. Hepatic inflammation also showed significant interactions for Il6 (p < 0.001) and Tnfa (p = 0.003). In addition, the sucralose group exhibited heightened neuroinflammation, cerebral endoplasmic reticulum stress, and increased depressive-like behaviors. 16S rRNA sequencing demonstrated reduced α-diversity and a shift in microbial composition and predicted carbohydrate processing and transport functions. Spearman correlation analysis linked microbial, intestinal, hepatic, neuroinflammatory, and behavioral variables within sucralose-treated mice. Conclusions: Long-term sucralose consumption altered gut microbial composition, hepatic cholesterol regulation, and neuroinflammatory and behavioral outcomes.

Nutrients doi: 10.3390/nu18203451

Authors: Terese M. Zidon Jaume Padilla Leighton T. McCabe Olivia E. Stricklin Young-Min Park Dennis B. Lubahn Victoria J. Vieira-Potter

Loss of ovarian hormones leads to obesity and insulin resistance (IR), increasing the risk of cardiovascular and metabolic diseases. We previously showed that aged female ERa knockout (αKO) and ERb knockout (βKO) mice differentially respond to ovariectomy, with a greater adverse metabolic response in βKO mice. We later showed that young ovariectomized (OVX) βKO mice were somewhat resistant to exercise-mediated metabolic benefits including adipose tissue browning. Background/Objectives: We tested the hypothesis that feeding a high phytoestrogen soy-based diet (SOY) would improve metabolic health in older OVX female mice and that αKO and βKO mice would differentially respond to the diet. Since phytoestrogens weakly bind ERs, and it is known that activation of ERa mediates insulin sensitizing and weight loss benefits, and ERb is known to improve adipocyte mitochondrial responses, we hypothesized that αKO mice would be less responsive to the systemic metabolic benefits of SOY, whereas βKO mice would be less responsive to adipocyte-specific benefits. Methods: We examined OVX and ovary-intact aged (~1 yr) wildtype (WT), αKO, and βKO female mice (n = 7–12/group). One week following OVX, mice were randomized to receive either SOY (585 mg phytoestrogens/kg) or a phytoestrogen-free diet (<15 mg/kg, CON) and were followed for 11 weeks. Mice were assessed for body composition (EchoMRI), energy expenditure (EE via Promethion metabolic cage system), glucose tolerance (i.p. glucose tolerance test), insulin sensitivity (HOMA-IR, Adipo-IR), adipose tissue gene and protein expression for insulin signaling markers, and fasting blood lipids. To provide additional mechanistic insight, primary adipocytes were treated with phytoestrogens and assessed for insulin-mediated phosphorylation of Akt. Results: Era mediated important metabolic benefits of SOY in aged OVX mice. OVX αKO mice were unresponsive to SOY-mediated improvements in body composition and glucose tolerance, whereas SOY improved those metrics, as well as increased spontaneous physical activity in OVX WT and βKO mice (all p < 0.05). Primary adipocyte cell culture experiments revealed that insulin-mediated phosphorylation of Akt occurred even with ERα-antagonization, with no effects of estrogen or phytoestrogen treatment, at least in the small set of experiments performed. Conclusions: SOY improved body composition and glucose tolerance in old OVX mice, effects that were absent in ERα-null mice. Soy-based diets may improve metabolic health in settings of ovarian hormone suppression via mechanisms requiring estrogen signaling pathway activation.

Nutrients doi: 10.3390/nu18203450

Authors: James Chmiel Donata Kurpas

Introduction: Background: Anorexia nervosa (AN) is associated with severe dietary restriction and multisystem effects of undernutrition, but biochemical micronutrient status does not necessarily parallel dietary intake or body weight. This scoping review mapped biological evidence on vitamin, mineral, trace-element, and electrolyte status in AN. Methods: The review was structured using JBI scoping review methodology and is reported according to PRISMA-ScR. PubMed/MEDLINE, Scopus, Web of Science Core Collection, and supplementary Google Scholar searching were used from inception to 30 March 2026, together with backward reference-list screening. Eligibility was defined using the Population–Concept–Context framework. Original human studies containing a clearly identifiable AN population and reporting biological micronutrient markers were eligible; refeeding studies, case reports/series, and diagnostically mixed cohorts were retained when relevant but were distinguished from AN-specific comparative or cohort evidence. Data were charted by design, population, biological matrix, timing, and nutrient outcome and synthesized narratively. Results: Database searching identified 621 records; 109 studies met eligibility criteria, and reference-list screening added 27 studies, yielding 136 included sources. Findings were heterogeneous and did not support universal biochemical depletion. Phosphorus was frequently preserved at admission but declined during refeeding in many cohorts. Potassium, sodium, and magnesium abnormalities were most evident in medically unstable, purging, or refeeding contexts. Serum calcium was commonly preserved despite impaired bone health. Iron deficiency was uncommon in many cohorts despite anemia and altered ferritin, transferrin, or hepcidin. Selenium, zinc, and vitamin D were recurrently low in several studies, whereas vitamin B12 was more often normal or elevated than deficient. Conclusions: AN is characterized by context-dependent micronutrient dysregulation rather than uniform deficiency. Interpretation should account for study design, illness stage, purging behavior, supplementation, refeeding, biological matrix, and the limitations of circulating biomarkers. Normal serum or plasma concentrations do not necessarily exclude depleted tissue stores, functional insufficiency, or refeeding risk. Interpretation is prioritized by study design, sample size, biological matrix and treatment stage rather than numerical direction-of-finding counts. This review maps monitoring-relevant abnormalities but does not establish the efficacy of supplementation strategies.

Nutrients doi: 10.3390/nu18203449

Authors: Tomaso Oliaro Federico Amianto

Background/Objectives: Childhood obesity is a chronic, multifactorial disease requiring attention to biological, behavioral, psychological, family, and socioeconomic factors. This narrative review examined the integration of lifestyle, family-based, psychological, and pharmacological approaches, focusing on treatment engagement, eating disorders, attention-deficit/hyperactivity disorder (ADHD), and treatment durability. Methods: A single search interface covering PubMed/MEDLINE, Scopus, and Web of Science (the University of Turin library discovery platform) was used to identify studies published primarily from 2010 to August 2026. Pediatric trials, observational studies, systematic reviews, meta-analyses, guidelines, and public-health reports were prioritized. Results: Intensive family-based, multicomponent behavioral treatment remains the best-supported foundation of care, although psychological outcomes are infrequently assessed. Psychiatric comorbidity is heterogeneous; loss-of-control eating, emotional symptoms, ADHD, and executive-function difficulties may impair engagement in selected patients, and untreated ADHD has been associated with a slower BMI response to weight management. Professionally supervised obesity treatment containing a dietary component did not, on average, worsen eating psychopathology and reduced several related symptoms. Family participation improved outcomes, whereas logistical, socioeconomic, and psychological barriers reduced attendance. Across randomized trials, adding anti-obesity medication to behavioral treatment produced an additional, although on average modest, reduction in BMI. Semaglutide, liraglutide, and phentermine/topiramate produced larger numerical reductions than older agents in separate trials, but heterogeneity and the absence of head-to-head comparisons preclude formal ranking. Gastrointestinal adverse events were frequent with glucagon-like peptide-1 (GLP-1) receptor agonists. Pediatric trials and real-world evidence indicate partial weight regain after discontinuation, while prescribing remains limited and unequal. Conclusions: Pediatric obesity care should be phenotype-informed, multidisciplinary, and longitudinal. Pharmacotherapy can enhance BMI reduction but should complement rather than replace behavioral, psychological, and family care. Outcomes should extend beyond BMI to metabolic, psychological, functional, and long-term measures.

Nutrients doi: 10.3390/nu18203448

Authors: Jin-Hwan Oh Yoo-Seok Cheong Seong-Hoon Lim Seong Lee Jin-Hee Kim Hyuna Jang Youl Hour Vladimir Vuksan Hyang-Im Baek

Background/Objectives: Ginsenoside Rg3, a bioactive component of processed Korean ginseng, has demonstrated vasodilatory and blood pressure-lowering effects; however, clinical evidence on the long-term effects of Rg3-enriched ginseng preparations remains limited. This study evaluated the effects of two differently processed Rg3-enriched Korean ginseng preparations on blood pressure in adults with early-stage hypertension. Methods: In this 12-week, randomized, double-blind, placebo-controlled trial, 90 adults were randomly assigned to vitamin C-treated white ginseng (VTWG), enzyme-treated red ginseng (ETRG), or placebo (n = 30 per group). Both interventions provided approximately 40 mg/day of Rg3. Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were primary outcomes. Results: From baseline to week 12, SBP decreased by 7.27 ± 6.15 mmHg in the VTWG group and 9.86 ± 6.47 mmHg in the ETRG group, whereas it increased by 5.03 ± 6.52 mmHg in the placebo group (both adjusted p < 0.0001 vs. placebo). DBP decreased by 5.27 ± 5.58 and 6.32 ± 5.55 mmHg in the VTWG and ETRG groups, respectively, compared with a decrease of 0.90 ± 6.31 mmHg in the placebo group (adjusted p = 0.006, 0.0006, respectively). MAP also decreased significantly in both intervention groups compared with placebo (both adjusted p < 0.0001), whereas NO changes differed significantly only between ETRG and placebo (adjusted p = 0.017). No clinically meaningful safety concerns were identified. Conclusions: Twelve-week supplementation with either Rg3-enriched Korean ginseng preparation significantly reduced blood pressure compared with placebo, suggesting potential benefits for blood pressure management in adults with early-stage hypertension.

Nutrients doi: 10.3390/nu18203447

Authors: Anca Georgiana Ispas Alexandra Lacurezeanu Alina-Ioana Forray Andreea Rusu Dumitru Petreuș Răzvan Mircea Cherecheș

Background/Objectives: No study has evaluated a gamified nutrition-education platform for adolescents in Eastern Europe. This pilot study described short-term changes in nutrition literacy, dietary engagement and reported food habits after one session with AHOPE, an automated gamified platform, among Romanian adolescents. Methods: In a single-arm pre–post study, 332 adolescents aged 10–19 years began one session and 155 (46.7%) completed it, answering three scales, including an adapted forced-choice Adolescent Food Habits Checklist, immediately before and after. Paired tests used Benjamini–Hochberg correction; moderation and predictor analyses were exploratory. Results: All six outcome scores were higher after the session (all p_BH < 0.001; dz 0.42–0.73, largest for nutrition literacy). Of 23 food-habit items, 17 shifted toward the healthier response, with the largest shifts for the foods taught in the modules. Interaction tests gave no evidence that change differed by sex, age band or family affluence (all p_BH ≥ 0.90), although power was limited (low-affluence group, n = 18). Conclusions: Among completers, who were more affluent than non-completers, self-reported nutrition literacy, dietary engagement and food-habit responses were higher immediately after one session. These changes may reflect short-term intentions; the design cannot establish causation, persistence or behavioural change, which require a controlled trial with delayed follow-up.

Nutrients doi: 10.3390/nu18203446

Authors: Ken-ichiro Minato Miho Chikazawa Kyoka Unno Yoshie Yamana Takashi Tagawa Hiroshige Kuwahara Masashi Mizuno

Background/Introduction: The oral administration of Lactiplantibacillus plantarum 22A-3 (LP22A-3) could suppress ear inflammatory edema in the mice sensitized with an allergy-induced chemical compound, 1-fluoro-2, 4-dinitrobenzene (DNFB). Method: In this study, we formulated a hypothesis that the homeostasis of immunocompetent cells might be associated with alleviating this inflammation. Results: Pro-/anti-inflammatory cytokines are involved in the cell differentiation in vitro. Our results showed that the accumulation of pro-inflammatory cytokines, TNF-α and IL-6 were attenuated by the administration of the LP22A-3, in which bacteria were inactivated by heating at 80 °C. On the other hand, the level of the anti-inflammatory one, IL-10, was maintained. These findings suggested that LP22A-3 could be induced to build anti-inflammatory conditions. Regarding the cell migration from the small intestine, we aimed to clarify the mechanism in more detail by conducting experiments using KikGR mice to track the migration of target cells. We found that the migration of CD11b+CD86+ cells from the ileum increased in the DNFB-induced allergic dermatitis in mice. Then, the oral LP22A-3 administration could reduce their levels in the ileum to baseline levels. On the other hand, the migration of CD11b+CD206+ cells was enhanced in the dermatitis mice. However, it was shown that the increase in migration of those cells was not influenced by the LP22A-3 administration. Furthermore, our results suggested that oral LP22A-3 administration inhibited the differentiation of CD4+ cells into IL-9-inducing cells. Conclusions: This study might show the potential of immunocompetent cell action for alleviating the inflammation. In addition, the oral LP22A-3 administration could be a promising alternative alleviative strategy for type-IV allergic disorders.

Nutrients doi: 10.3390/nu18203445

Authors: Junho Yang Jinyoung Lee Hyunji Og Minsoo Jeong Seungjun Lee

Background/Objectives: Care-seeking for precocious puberty (PP) in South Korea has risen sharply, coinciding with dietary westernization among children. This study describes sex-specific and temporal dietary trends among Korean children aged 1–11 years, focusing on the 6–11-year band preceding the typical PP diagnosis threshold. Methods: Using KNHANES (2017–2021) dietary data and HIRA care-seeking counts with the sex-year aggregate, not the individual child. Sex differences were assessed using the Mann–Whitney U test, year-to-year patterns using a sex-by-year interaction model (n = 5 annual observations per sex), and dietary pattern structure using principal component analysis (PCA) on 12 food groups (n = 10 sex-year observations). Results: PP care-seeking rates rose in both sexes, substantially more in girls. Boys showed significantly higher intake of most food groups and macronutrients; within the 6–11-year band this held for meat, cola, and macronutrients (p = 0.008) but not legumes (p = 0.421). Macronutrient sex gaps numerically narrowed while meat and cola gaps widened over 2017–2021, though none reached significance. PCA identified a primary axis reflecting overall intake volume that separated boys and girls, and a secondary axis distinguishing a dairy/seaweed/beverage profile from a meat/egg/cola-dominant profile. Conclusions.: These findings describe sex-specific dietary patterns amid rising PP rates without establishing that intake volume explains the sex disparity, identifying candidate exposures for future research and cautioning against oversimplified dietary narratives.

Nutrients doi: 10.3390/nu18203443

Authors: Yining Chen Megan Gow Katie Harris Lynne Roberts Alison Canty Wendy Pickup Natasha Hirschhorn-Edwards Amanda Henry

Background/Objectives: Postpartum lifestyle interventions may mitigate increased cardiovascular disease (CVD) risks following hypertensive disorders of pregnancy (HDP). The study aimed to examine longitudinal changes in post-HDP lifestyle behaviors and women’s perceptions towards healthy living. Methods: This study was a longitudinal sub-study of the 3-armed, multicenter Blood Pressure Postpartum (BP2) randomized controlled trial in post-HDP women, comprising different postpartum care/lifestyle intervention strategies 6–12 months postpartum and post-intervention observational follow-up to 3–4 years postpartum. The NSW Health Population Survey captured lifestyle variables 6–12 months postpartum. At 3–4 years post-HDP, the Australian Eating Survey and the International Physical Activity Questionnaire were alternatively used for diet and physical activity, respectively. Linear mixed-effects models analyzed daily consumption of vegetables/fruit, moderate-to-vigorous physical activity (MVPA), and perception scores of healthy living for motivators, barriers, and satisfaction. Results: In 180 participants, reported mean (SD) vegetable/fruit daily intake increased (vegetable servings/day: 2.6 (1.3), 6 months vs. 2.7 (1.4), 12 months vs. 4.2 (2.0), 3–4 years, p < 0.001; fruit servings/day: 1.7 (1.0), 6 months vs. 1.7 (1.0), 12 months vs. 2.2 (1.3), 3–4 years, p < 0.001), while accompanied by other unfavorable dietary changes. Reported median [IQR] MVPA increased (minutes/week, 330 [280], 6 months vs. 313 [331], 12 months vs. 515 [690], 3–4 years, p < 0.001). Motivators to engage in healthy behaviors decreased (p < 0.001), perceived barriers increased (p < 0.001), and satisfaction with diet and body appearance worsened over time (p < 0.001). Conclusions: Overall, women reported higher intake of both health-promoting and less health-promoting foods and higher MVPA; however, different tools were used for lifestyle measurement. Worsening perceptions were observed using the same instrument.

Nutrients doi: 10.3390/nu18203444

Authors: Gonca Yildirim Esra Tansu Sariyer Ekin Çevik Betül Çiçek

Background: Ultra-processed foods (UPFs) are becoming more common in children’s dietary habits, yet little is known about products marketed specifically to children in Türkiye. This research assessed the frequency, geographic differences, and energy-standardized cost of UPFs targeted at children. Methods: This cross-sectional study identified 340 food and beverage products aimed at children in six Turkish cities with varying regional income levels. We categorized items according to the NOVA framework. The prevalence of UPFs was analyzed by different cities, and the cost per 100 kcal was assessed between UPFs and non-UPFs. Results: Overall, 66.8% of products were classified as UPFs. Prevalence ranged from 53.3% to 83.7% across cities and differed significantly by product category. All milks, confections, and custards were UPFs of childhood. Most fruit and vegetable purees were not UPFs. The main markers of ultra-processing were added sugars, emulsifiers, and flavorants. The median cost for every 100 kcal was lower for UPFs than for non-UPFs (21.45 vs. 67.47 TRY, p < 0.001). After controlling for study city, non-UPFs had 2.87 times higher costs per 100 kcal than UPFs (95% CI: 2.27–3.62), but this association was not significant after further controlling for product category. Conclusions: UPFs were widely available in products marketed to children in Türkiye, with significant variation between product categories and regions. The lower cost per 100 kcal appeared to reflect differences in product composition across categories.

Nutrients doi: 10.3390/nu18203442

Authors: Mevra Aydin Cil Neva Karatas Fatma Betül Ozgeris Esen Tasgin Serap Sari Rüveyda Esra Özkalaycı

Background: Advanced glycation end products (AGEs) may link diet, systemic inflammation, and cognitive function; however, evidence in healthy young adults is limited. Objective: This study aimed to examine the associations of dietary AGE (dAGE) intake, circulating AGE–RAGE biomarkers, inflammation, and oxidant–antioxidant markers with cognitive performance. Methods: This cross-sectional study included healthy young adults aged 19–26 years. dAGE intake was estimated using a food-frequency questionnaire (FFQ) and a three-day food record (3D-FR). Serum AGEs (sAGEs), soluble RAGE (sRAGE), interleukin-6, tumour necrosis factor-alpha (TNF-α), malondialdehyde, catalase, superoxide dismutase, and glutathione were measured. Cognitive performance was assessed using Digit Span Forward, Backward, and Total scores and Stroop Interference. Separate multivariable linear regression models were adjusted for age, sex, body mass index, and Beck Depression Inventory-II scores, with Benjamini–Hochberg false-discovery-rate correction. Covariate-adjusted partial least squares structural equation modelling (PLS-SEM) examined the prespecified sAGE–sRAGE–inflammation pathways. Results: In the correlation analyses, dAGE intake estimated using the FFQ and 3D-FR was not significantly associated with sAGE concentrations (p > 0.05). In the separate regression models, higher sAGEs (β = −0.36, 95% CI −0.54 to −0.16) and TNF-α (β = −0.33, 95% CI −0.53 to −0.13) were associated with poorer Digit Span Backward performance after false-discovery-rate correction. No other cognitive associations remained significant. In PLS-SEM, sAGEs were positively associated with sRAGE (β = 0.505, p < 0.001), and sRAGE was positively associated with inflammation (β = 0.601, p < 0.001). Greater inflammation was associated with poorer Digit Span Backward performance (β = −0.398, 95% CI −0.697 to −0.110, p = 0.009), whereas the direct sRAGE–Digit Span Backward path was not significant. An indirect inverse association between sRAGE and Digit Span Backward through inflammation was supported (β = −0.239, 95% bootstrap CI −0.457 to −0.057). Conclusions: In conclusion, higher circulating sAGEs and TNF-α concentrations were associated with poorer working-memory performance, particularly on Digit Span Backward, in healthy young adults, whereas estimated dAGE intake showed no significant associations with cognitive performance. Longitudinal studies with larger samples are needed to establish temporality and confirm the significance of these associations.

Nutrients doi: 10.3390/nu18203441

Authors: Qinshuo Zhang Honghan Xu Junli Mo Fucong Wang Xing Gao Chengyu Zhou Zhuo Zeng Xusong Dong Dongxu Huang Haoqiang Shi Haoran Li Kai Gao Yongmin Xie Aiguo Zhou Diandong Lang Bingbing He

Background: This systematic review and exploratory meta-analysis evaluated the effects of combined music and caffeine on psychophysiological responses during exercise. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched from database inception to 10 June 2026. Randomized crossover studies comparing caffeine plus music with placebo plus no music, caffeine alone, or music alone were eligible. Outcomes included rating of perceived exertion (RPE), Physical Activity Enjoyment Scale (PACES), Feeling Scale (FS), and heart rate (HR). Findings were synthesized descriptively by outcome and comparator, considering study-specific effect estimates, confidence intervals, and experimental conditions. Random-effects meta-analyses were retained as secondary exploratory summaries. Because fewer than 10 independent studies were available, meta-regression and formal assessment of small-study effects were not undertaken. Results: Five crossover studies involving 88 participants were included. Study-specific RPE estimates varied from large reductions to estimates close to the null or in the opposite direction. PACES point estimates favoured the combined intervention, but their magnitudes differed substantially in comparisons with placebo plus no music and caffeine alone. Feeling Scale and heart-rate findings also varied across studies. All four primary meta-analyses showed I2 values exceeding 90%, and the certainty of evidence was very low for all primary outcomes. Conclusions: The available evidence comprises five small crossover studies conducted in different populations and experimental settings. Study-specific findings suggest possible improvements in exercise enjoyment, while perceived exertion, affective valence, and heart-rate responses vary across studies. Neither the descriptive findings nor the secondary exploratory pooled estimates establish a stable, broadly applicable magnitude of intervention benefit. Given the very low certainty of evidence, no firm recommendations can be made regarding the use of caffeine combined with music across exercise populations and settings. Further adequately powered studies using clearly specified interventions and comparable outcome assessments are needed to determine which responses are reproducible and practically meaningful.

Nutrients doi: 10.3390/nu18203440

Authors: Roberta Cianci Domenica Francesca Mariniello Giuseppe Luciano Filippo Scialò Luigi Aronne Grazia Mazzeo Alfredo Cipriano Susan F. Campbell Fabio Perrotta Andrea Bianco Raffaella Pagliaro

Background/Objectives: Skeletal muscle wasting is a frequent and clinically consequential comorbidity in COPD, affecting 15–50% of patients and predicting reduced exercise tolerance, impaired quality of life, hospitalization, and mortality. However, no consensus exists on the optimal diagnostic approach, and the role of nutritional assessment remains underemphasized despite its contribution to muscle depletion. Methods: This narrative review synthesizes evidence from original research, systematic reviews, and consensus statements on diagnostic methods for evaluating muscle mass, strength, physical performance, and nutritional status in COPD. Results: Computed tomography and magnetic resonance imaging offer accurate assessment of muscle mass but are limited by cost and accessibility. Dual-energy X-ray absorptiometry provides a low-radiation alternative but cannot assess muscle quality. Bioelectrical impedance analysis and ultrasound are portable and inexpensive, yet lack standardized COPD-specific cut-offs. Functional tests provide clinically meaningful performance data but do not directly measure muscle mass. In parallel, nutritional screening tools and dietary assessment can identify modifiable risk factors and are associated with sarcopenia prevalence and prognosis in COPD. The choice of diagnostic approach significantly influences prevalence estimates. Conclusions: Optimal assessment of muscle wasting in COPD requires a multimodal approach combining muscle mass quantification, strength measurement, physical performance evaluation, and nutritional assessment. Standardized COPD-specific diagnostic criteria are needed. A practical algorithm integrating simple screening tools with targeted confirmatory assessments, including nutritional evaluation, may help guide clinical practice.

Nutrients doi: 10.3390/nu18203439

Authors: Demet Teker-Duztas İsa An

Background/Objectives: Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis characterized by oral and lingual involvement, frequently accompanied by dysphagia and recurrent oral ulcers. The relationships between these clinical manifestations and nutritional status or growth have not been clearly established. This study evaluated nutritional, growth, and micronutrient statuses in pediatric patients with LP and investigated their associations with dysphagia, oral ulcer frequency, and a composite oral involvement score. Methods: This prospective, cross-sectional, single-center study enrolled 30 pediatric patients with LP. Anthropometric measurements, laboratory results, and clinical data regarding oral involvement and dysphagia were collected. A study-specific composite oral involvement score (range: 0–4) was calculated based on restricted mouth opening, restricted tongue movement, presence of a thick or woody tongue, and active oral ulcers. Results: Mean age was 8.44 ± 4.97 years; 66.7% were male, and all had parental consanguinity. Mean HFA and WFH/BMI z-scores were −1.44 ± 1.07 and −0.55 ± 1.28; stunting and wasting occurred in 26.7% and 6.7%. Active oral ulcers and dysphagia were present in 70.0% and 60.0%. Iron-deficiency anemia (33.3%) and vitamin D deficiency (16.7%) were the most common deficiencies. Patients with dysphagia had lower HFA z-scores (p < 0.001; Cohen’s d = 1.91), which remained significant after Holm correction. The association between dysphagia and stunting did not remain significant after correction, and no other associations were found with dysphagia, oral ulcer frequency, or the composite oral involvement score. Conclusions: Dysphagia was associated with lower HFA z-scores in pediatric LP, whereas oral ulcer frequency and composite oral involvement were not. These exploratory findings suggest that swallowing function should be assessed during follow-up; larger multicenter prospective studies with standardized swallowing assessments are needed.

Nutrients doi: 10.3390/nu18203438

Authors: Emma Whatley Abigail Frommack Emily Bayliss Merritt Smith Seth Woodfin Ersilia Mirabelli Dane Fausnacht Kayla R. Gilley-Connor William Moore

Maternal nutrition is a key determinant of fetal development, particularly in the context of neural regulation and maturation. Omega-3 polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), play an essential role in neural differentiation, synaptogenesis, myelination, and neuroprotection. While the neurodevelopmental benefits of DHA are well-documented, the effects of excessive maternal DHA intake and the potential long-term consequences on offspring neurophysiology remain poorly understood. The purpose of this review is to synthesize current findings on the role of DHA in fetal neural development, emphasizing biochemical mechanisms and developmental outcomes. It further explores emerging concerns associated with excessive intake, the varied responses to intake, the varied sources of supplements, and the influence of maternal metabolic conditions, such as diabetes, on DHA bioavailability and fetal brain development. Finally, the review highlights the need for individualized supplementation strategies in maternal nutrition and considers the potential epigenetic implications of prenatal DHA exposure, to ultimately inform future research and therapeutic strategies in maternal–fetal health and neurodevelopmental biology.

Nutrients doi: 10.3390/nu18203436

Authors: Amaal Aldakheel Najeeb Qadi

Background/Objectives: Cognitive impairment affects most people with Parkinson’s disease (PD); mild cognitive impairment is present in 25–40% of people with PD without dementia, and nutritional advice often exceeds the evidence. We reviewed the human evidence that dietary patterns or nutritional supplements improve cognition in established PD, separating objective cognitive outcomes from patient-rated and biomarker outcomes. Methods: Critical narrative review reported according to SANRA. Sources were PubMed, Embase, Web of Science and Cochrane CENTRAL (inception to 29 September 2026) and reference lists. Controlled intervention studies in established idiopathic PD with an objective cognitive outcome or a specifically rated cognitive symptom formed the evidence set, appraised on risk-of-bias domains and classified by an explicit rule. Results: Twenty-three randomized controlled studies met the criteria (five dietary patterns, 18 supplements). Favorable between-group differences were reported in six studies (Mediterranean diet, a ketogenic pilot, creatine–coenzyme Q10, a probiotic, saffron and ginkgo leaf extract), all with fewer than 100 participants and heterogeneous cognitive endpoint status. The three largest trials did not demonstrate cognitive benefit. Other reports showed nonsignificant comparisons or did not provide a between-group cognitive estimate; one used only a rated symptom. No study showed durable functional benefit or reduced progression to dementia. Conclusions: No nutritional intervention has independently replicated, durable cognitive efficacy in PD. Nutritional adequacy, correction of documented deficiency, dysphagia care and individualized levodopa–meal timing remain the clinical priorities; a Mediterranean-style pattern is a reasonable default, not a cognitive treatment.